|
1
|
Sun RQ, Ye YH, Xu Y, Wang B, Pan SY, Li N, Chen L, Pan JY, Hu ZQ, Fan J, Zhou ZJ, Zhou J, Song CL, Zhou SL. Integrated molecular characterization of sarcomatoid hepatocellular carcinoma. Clin Mol Hepatol 2025; 31:426-444. [PMID: 39657751 PMCID: PMC12016616 DOI: 10.3350/cmh.2024.0686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/15/2024] [Accepted: 12/06/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUNDS/AIMS Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. METHODS In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. RESULTS Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial-mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1-5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. CONCLUSION We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
Collapse
Affiliation(s)
- Rong-Qi Sun
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yu-Hang Ye
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ye Xu
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Bo Wang
- Department of General Surgery, Second Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Si-Yuan Pan
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ning Li
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Long Chen
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jing-Yue Pan
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhi-Qiang Hu
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng-Jun Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Cheng-Li Song
- Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Shao-Lai Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
2
|
Sun RQ, Zhou SL. Correspondence to editorial on "Integrated molecular characterization of sarcomatoid hepatocellular carcinoma". Clin Mol Hepatol 2025; 31:e192-e193. [PMID: 40007141 PMCID: PMC12016595 DOI: 10.3350/cmh.2025.0183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 02/22/2025] [Indexed: 02/27/2025] Open
Affiliation(s)
- Rong-Qi Sun
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shao-Lai Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
3
|
Nishida N. Genetic insights into sarcomatoid hepatocellular carcinoma: Critical role of ARID2 in pathogenesis and immune feature: Editorial on "Integrated molecular characterization of sarcomatoid hepatocellular carcinoma". Clin Mol Hepatol 2025; 31:635-639. [PMID: 39849959 PMCID: PMC12016655 DOI: 10.3350/cmh.2025.0071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Accepted: 01/23/2025] [Indexed: 01/25/2025] Open
Affiliation(s)
- Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| |
Collapse
|
|
4
|
Gao B, Liu Y, Duan W. Sarcomatoid Hepatocellular Carcinoma: A Case Report and Review of Literature. Clin Case Rep 2025; 13:e70195. [PMID: 39935659 PMCID: PMC11810626 DOI: 10.1002/ccr3.70195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 12/23/2024] [Accepted: 01/29/2025] [Indexed: 02/13/2025] Open
Abstract
Sarcomatoid hepatocellular carcinoma (SHC), which contains variable proportions of sarcomatous and carcinomatous components, is a rare variant of hepatocellular carcinoma and is a special variant of hepatocellular carcinoma. It is highly malignant, progresses rapidly, and has an extremely poor prognosis. However, the molecular pathogenesis of SHC remains unknown. We report a case of a 35-year-old male, previously healthy with no liver disease history, who presented with intermittent fever. Imaging examination during hospitalization revealed focal liver lesions. Without obvious surgical contraindications, right hemihepatectomy, cholecystectomy, and regional lymph node dissection were performed. Postoperative pathology and immunohistochemistry confirmed the diagnosis of SHC. However, due to the financial burden of the disease, the patient and his family chose traditional Chinese medicine as postoperative supplementary treatment rather than targeted drug combined with immunotherapy or other adjuvant therapies. Unfortunately, the patient passed away due to tumor recurrence 8 months after surgery.
Collapse
Affiliation(s)
- Bo Gao
- Department of Hepatobiliary SurgeryAffiliated Hospital of Hebei UniversityBaodingChina
| | - Yan Liu
- Department of Hepatobiliary SurgeryAffiliated Hospital of Hebei UniversityBaodingChina
| | - Wendu Duan
- Department of Hepatobiliary SurgeryAffiliated Hospital of Hebei UniversityBaodingChina
| |
Collapse
|
|
5
|
Jin X, Wang Y, Chen J, Niu M, Yang Y, Zhang Q, Bao G. Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, and in vitro and in vivo biological activity evaluations. J Enzyme Inhib Med Chem 2024; 39:2289355. [PMID: 38059332 PMCID: PMC11721945 DOI: 10.1080/14756366.2023.2289355] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 11/02/2023] [Accepted: 11/26/2023] [Indexed: 12/08/2023] Open
Abstract
Liver cancer exhibits a high degree of heterogeneity and involves intricate mechanisms. Recent research has revealed the significant role of histone lysine methylation and acetylation in the epigenetic regulation of liver cancer development. In this study, five inhibitors capable of targeting both histone lysine methyltransferase nuclear receptor-binding SET domain 2 (NSD2) and histone deacetylase 2 (HDAC2) were identified using a structure-based virtual screening approach. Notably, DT-NH-1 displayed a potent inhibition of NSD2 (IC50 = 0.08 ± 0.03 μM) and HDAC2 (IC50 = 5.24 ± 0.87 nM). DT-NH-1 also demonstrated a strong anti-proliferative activity against various liver cancer cell lines, particularly HepG2 cells, and exhibited a high level of biological safety. In an experimental xenograft model involving HepG2 cells, DT-NH-1 showed a significant reduction in tumour growth. Consequently, these findings indicate that DT-NH-1 will be a promising lead compound for the treatment of liver cancer with epigenetic dual-target inhibitors.
Collapse
Affiliation(s)
- Xing Jin
- Department of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Yuting Wang
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China
| | - Jing Chen
- Department of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Miaomiao Niu
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China
| | - Yang Yang
- Department of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Qiaoxuan Zhang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guangyu Bao
- Department of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| |
Collapse
|
|
6
|
Feng X, Ma Y, Yang J, Peng P, Zeng X, Shen L, Hu T, Luo Q. Comparison of effects of different anesthesia methods on immune function and liver function of liver cancer patients after operation. Biotechnol Genet Eng Rev 2024; 40:2672-2682. [PMID: 37066843 DOI: 10.1080/02648725.2023.2201521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 04/06/2023] [Indexed: 04/18/2023]
Abstract
Liver cancer, one of the most common malignant tumors, has seriously threatened people's physical and mental health. The paper was conducted to investigate the functions of two different anesthesia methods on Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and T lymphocyte subsets in patients undergoing liver cancer resection, and to explore the liver function impact of patients undergoing liver cancer surgery. 80 liver cancer patients were split into propofol intravenous anesthesia group and sevoflurane inhalation anesthesia group. The patient's operation-related indicators and changes in TNF-α, CRP and T lymphocyte subsets before anesthesia, after anesthesia, 1 day after anesthesia, and 3 days after anesthesia were calculated. The levels of TNF-α and CRP in the two groups after operation were clearly higher than those before anesthesia, but there was no obvious difference between the two groups. After operation, the TNF-α of the propofol intravenous anesthesia group was lower than the sevoflurane inhalation anesthesia group. The CD3+, CD4+ and CD4+/CD8+ levels in both groups recovered to the pre-anaesthesia level 3 days after the operation. The levels of ALT, AST, ALB and TBIL returned to normal at d4 in both propofol intravenous anesthesia and sevoflurane inhalation anesthesia groups. Compared with evoflurane inhalation anesthesia for patients with liver cancer, intravenous anesthesia with propofol can reduce the body's inflammatory response to a certain extent, has weak inhibitory effect on T lymphocyte immune function, and a smaller effect on liver function.
Collapse
Affiliation(s)
- Xi Feng
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Yao Ma
- Department of Anesthesiology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuchang, China
| | - Jun Yang
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Pai Peng
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Xiaohua Zeng
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Lei Shen
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Tingting Hu
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Qin Luo
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| |
Collapse
|
|
7
|
Numata Y, Akutsu N, Idogawa M, Wagatsuma K, Numata Y, Ishigami K, Nakamura T, Hirano T, Kawakami Y, Masaki Y, Murota A, Sasaki S, Nakase H. Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma. Hepatol Res 2024; 54:859-865. [PMID: 38459823 DOI: 10.1111/hepr.14034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 02/05/2024] [Accepted: 02/17/2024] [Indexed: 03/10/2024]
Abstract
A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.
Collapse
Affiliation(s)
- Yuto Numata
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Noriyuki Akutsu
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masashi Idogawa
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Medical Genome Sciences, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Kohei Wagatsuma
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yasunao Numata
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keisuike Ishigami
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tomoya Nakamura
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takehiro Hirano
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yujiro Kawakami
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yoshiharu Masaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ayako Murota
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shigeru Sasaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| |
Collapse
|
|
8
|
Chhabra R, Vidushi A, Rajpurohit S, Singh J, Osama MA. Spontaneous Tumor Lysis Syndrome in a Case of Hepatocellular Carcinoma with Sarcomatoid Differentiation. Indian J Surg Oncol 2024; 15:370-374. [PMID: 38741637 PMCID: PMC11088581 DOI: 10.1007/s13193-024-01895-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 02/02/2024] [Indexed: 05/16/2024] Open
Abstract
Sarcomatoid hepatocellular carcinoma is a rare histologic variant of primary liver cancer comprising of malignant spindle cells and typical hepatocellular carcinoma (HCC). In terms of clinical presentation, they usually exhibit extensive tumor burden due to their larger size and a metastatic disease at the time of diagnosis as compared to conventional HCC. Tumor lysis syndrome is an oncological emergency, usually seen after cytotoxic chemotherapy in haematological malignancies. Here, we highlight a case of 76-year old male with no comorbidities, presenting with an excruciating backache and a paravertebral soft tissue mass and multiple osteolytic lesions, was clinically suspected to be a plasma cell neoplasm. On further evaluation, the patient was diagnosed of a sarcomatoid variant of hepatocellular carcinoma. This report showcases multiple rare findings by the presence of non-specific symptoms, non-cirrhotic liver, normal serum alpha protein levels and the occurrence of a spontaneous tumor lysis syndrome in a solid malignancy.
Collapse
Affiliation(s)
- Raja Chhabra
- Department of Medical Oncology, BLK-MAX Super Speciality Hospital, Pusa Road, New Delhi, India
| | - Aditya Vidushi
- Department of Medical Oncology, BLK-MAX Super Speciality Hospital, Pusa Road, New Delhi, India
| | - Sajjan Rajpurohit
- Department of Medical Oncology, BLK-MAX Super Speciality Hospital, Pusa Road, New Delhi, India
| | - Jasbir Singh
- Department of Pathology, BLK-MAX Super Speciality Hospital, Pusa Road, New Delhi, India
| | - Md Ali Osama
- Department of Pathology, Lady Hardinge Medical College, New Delhi, India
| |
Collapse
|
|
9
|
Radhakrishnan S, Martin CA, Vij M, Subbiah K, Raju LP, Gowrishankar G, Veldore VH, Kaliamoorthy I, Rammohan A, Rela M. Treatment and prognostic implications of strong PD-L1 expression in primary hepatic sarcomatoid carcinoma. Immunotherapy 2024; 16:371-379. [PMID: 38362631 DOI: 10.2217/imt-2023-0243] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 01/26/2024] [Indexed: 02/17/2024] Open
Abstract
Primary hepatic sarcomatoid carcinoma (HSC) is an extremely rare and aggressive subtype of primary liver cancer. HSC has uncertain pathogenesis and dismal prognosis with overall survival of only 8.3 months. The molecular alterations of HSC are also not well understood. In this study, the authors describe a patient who presented with a large liver mass. The patient underwent complete surgical resection and histological examination demonstrated HSC, infiltrating the stomach. PD-L1 was strongly positive in the tumor cells. The patient was started on anti-PD-L1 immunotherapy postsurgery and is doing well 15 months after surgical resection. Tumor whole exome sequencing revealed genetic alterations in TP53, NF2 and MAGEC3 genes, indicating their potential role in tumor development.
Collapse
Affiliation(s)
- Subathra Radhakrishnan
- Cell Laboratory, National Foundation for Liver Research, No. 7 CLC Works Road, Chromepet, Chennai-44, Tamil Nadu, India
| | - Catherine Ann Martin
- Cell Laboratory, National Foundation for Liver Research, No. 7 CLC Works Road, Chromepet, Chennai-44, Tamil Nadu, India
| | - Mukul Vij
- Department of Pathology, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai-44, Tamil Nadu, India
| | - Komalavalli Subbiah
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai-44, Tamil Nadu, India
| | - Lexmi Priya Raju
- Department of Pathology, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai-44, Tamil Nadu, India
| | - Gowripriya Gowrishankar
- Department of Pathology, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai-44, Tamil Nadu, India
| | - Vidya Harini Veldore
- 4baseCare Onco Solutions Pvt Ltd, IBAB campus, Bangalore Helix Biotech Park, Bangalore-100, Karnataka, India
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai-44, Tamil Nadu, India
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai-44, Tamil Nadu, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai-44, Tamil Nadu, India
| |
Collapse
|
|
10
|
Yoshida T, Sakai K, Kaibori M, Ishida M, Tanaka S, Kubo S, Nakai T, De Velasco MA, Matsushima H, Tsuta K, Sekimoto M, Nishio K. Downregulated expression of PBRM1 in sarcomatoid hepatocellular carcinoma. Oncol Lett 2024; 27:124. [PMID: 38348389 PMCID: PMC10859838 DOI: 10.3892/ol.2024.14257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 01/03/2024] [Indexed: 02/15/2024] Open
Abstract
Sarcomatoid hepatocellular carcinoma (SHCC) is a rare and highly lethal subtype of HCC. The present study aimed to explore the unique markers of SHCC using whole gene expression analysis. Subsequently, gene expression analysis was performed using five sarcomatoid and seven carcinomatoid components of seven tissues from patients with SHCC. The results demonstrated a significant downregulation of polybromo 1 (PBRM1) gene expression in the sarcomatoid components. Immunohistochemical staining also indicated a decreased expression of PBRM1 in the sarcomatoid components. Moreover, gene ontology enrichment analysis revealed that most of the 336 differentially expressed genes between the sarcomatoid and carcinomatoid components were involved in functions associated with DNA replication and histone methylation, which was consistent with the loss of function of PBRM1 which encodes Switch/sucrose-non-fermentable chromatin remodeling complex protein. Therefore, the results of the present study suggested that PBRM1 may be a candidate biomarker for the evaluation of SHCC.
Collapse
Affiliation(s)
- Terufumi Yoshida
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Kazuko Sakai
- Department of Genome Biology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
| | - Masaki Kaibori
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Mitsuaki Ishida
- Department of Pathology, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka 569-8686, Japan
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka 545-8585, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka 545-8585, Japan
| | - Takuya Nakai
- Department of Surgery, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
| | - Marco A. De Velasco
- Department of Genome Biology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
| | - Hideyuki Matsushima
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Koji Tsuta
- Department of Pathology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Kazuto Nishio
- Department of Genome Biology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
| |
Collapse
|
|
11
|
Zhao Q, Ji Z, Chen Y, Wang K, Qiu Y, Tian X, Zhu Y, Qin H, Han H, Yuan H, Dong Y, Wang W. Contrast-enhanced ultrasound features of hepatic sarcomatoid carcinoma different from hepatocellular carcinoma. Clin Hemorheol Microcirc 2024; 87:55-65. [PMID: 38160348 DOI: 10.3233/ch-231944] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
BACKGROUND Hepatic sarcomatoid carcinoma (HSC) is a rare malignancy of the liver. The ultrasound and clinical features of HSC have not been determined. OBJECTIVE To investigate and compare the ultrasound and clinical features of HSC and hepatocellular carcinoma (HCC), and to reveal the valuable features of HSC. METHODS The ultrasound features and clinical data of pathologically proven HSC (n = 37) were compared with HCC (n = 92) in a matching ratio of 1:4 using the propensity score (age, gender and tumor size). RESULTS The HSC patients were more likely to accompany with clinical symptoms and vascular invasion than HCC patients (40.5% vs 17.4%, 24.3% vs 6.5%, P < 0.05). The size of HSCs was significantly larger than that of HCCs (P < 0.05). The proportion of patients with elevated alpha-fetoprotein was significantly lower in HSC (35.1% vs 54.3%, P < 0.05). On gray-scale ultrasound images, the HSCs were more likely to demonstrate as indistinct margin and irregular shape lesions compared to HCCs (78.4% vs 48.8%; 70.3% vs 23.9%, P < 0.05). Under color Doppler flow imaging (CDFI), the blood flow signals were more frequently detected in HSC lesions (75.7% vs 56.5%, P < 0.05). Resistance index (RI) was higher in HSCs than in HCCs [0.78 (0.70,0.82) vs 0.70 (0.62,0.76), P < 0.05]. On contrast-enhanced ultrasound (CEUS), HSCs mainly showed entirety heterogeneous hyper-enhancement (48.6%), entirety homogeneous enhancement (18.9%), peripheral and internal septal enhancement (18.9%). The incidence of non-enhanced areas inside HSC lesions was higher than that inside HCC lesions (56.8% vs 31.5%, P < 0.05). During the portal venous and late phases, most of the lesions revealed hypo-enhancement in both groups, whereas earlier washout was observed in HSCs [43.0 s (30.5,58.0) vs 60.0 s (46.3,100.0), P < 0.05]. CONCLUSIONS CEUS features are useful in preoperative and non-invasive differentiation of hepatic sarcomatoid carcinoma and hepatocellular carcinoma.
Collapse
Affiliation(s)
- Qiannan Zhao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhengbiao Ji
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yanling Chen
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kun Wang
- Department of Ultrasound, Binzhou Medical University Hospital, Binzhou, China
| | - Yijie Qiu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaofan Tian
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuli Zhu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hong Qin
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hong Han
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haixia Yuan
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Ultrasound, Zhongshan Hospital, Fudan University (Qingpu Branch), Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Imaging Medicine, Shanghai, China
| |
Collapse
|
|
12
|
Morisue R, Kojima M, Suzuki T, Watanabe R, Sakamoto N, Sakashita S, Harada K, Nakai T, Ishii G, Nakatsura T, Gotohda N, Ishikawa S. Common clinicopathological and immunological features of sarcomatoid carcinoma across organs: A histomorphology-based cross-organ study. Int J Cancer 2023; 153:1997-2010. [PMID: 37548077 DOI: 10.1002/ijc.34680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 06/25/2023] [Accepted: 07/20/2023] [Indexed: 08/08/2023]
Abstract
Sarcomatoid carcinoma (SC), which can occur in any organ, is a rare disease. To elucidate common characteristics of SC beyond organs, we evaluated clinicopathological and immunological features of SC defined by the single histological criterion beyond organs compared to randomly matched conventional carcinoma (non-SC) adjusted for the disease stage. Immunological features were assessed by multiplex immunohistochemistry, comparing immune cell density in tumor tissues and tumor programmed death-ligand 1 (PD-L1) expression. A total of 101 patients with SC or non-SC (31 lung, 19 esophagus, 22 pancreas, 15 liver, 4 bile duct, 6 kidney, 2 uterus and 2 ovary) were identified among 7197 patients who underwent surgery at our institute (1997-2020). SC was significantly associated with worse survival (HR: 1.571; 95% CI: 1.084-2.277; P = .017). The frequency of postoperative progression within 6 months was significantly higher for SC patients (54% vs 28%; P = .002). The immune profiling revealed the densities of CD8+ T cells (130 vs 72 cells/mm2 ; P = .004) and tumor-associated macrophages (566 vs 413 cells/mm2 ; P < .0001) and the tumor PD-L1 expression score (40% vs 5%; P < .0001) were significantly higher in SCs than in non-SCs. Among 73 SC patients with postoperative progression, multivariate Cox regression analysis showed that immunotherapy tended to be associated with favorable survival (HR: 0.256; 95% CI: 0.062-1.057; P = .060). Collectively, SCs shared clinicopathological and immunological features across organs. Our study can initiate to standardize the pathological definition of SC and provide a rationale for the investigation and development for this rare disease in a cross-organ manner.
Collapse
Affiliation(s)
- Ryo Morisue
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Motohiro Kojima
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
| | - Toshihiro Suzuki
- Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
- Division of Pharmacology, School of Medicine, Teikyo University, Tokyo, Japan
| | - Reiko Watanabe
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan
| | - Naoya Sakamoto
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
| | - Shingo Sakashita
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
| | - Kenji Harada
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
- Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tokiko Nakai
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan
| | - Genichiro Ishii
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan
| | - Tetsuya Nakatsura
- Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
| | - Naoto Gotohda
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Shumpei Ishikawa
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
- Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
13
|
van der Meeren PE, de Wilde RF, Sprengers D, IJzermans JNM. Benefit and harm of waiting time in liver transplantation for HCC. Hepatology 2023:01515467-990000000-00646. [PMID: 37972979 DOI: 10.1097/hep.0000000000000668] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/26/2023] [Indexed: 11/19/2023]
Abstract
Liver transplantation is the most successful treatment for limited-stage HCC. The waiting time for liver transplantation (LT) can be a critical factor affecting the oncological prognosis and outcome of patients with HCC. Efficient strategies to optimize waiting time are essential to maximize the benefits of LT and to reduce the harm of delay in transplantation. The ever-increasing demand for donor livers emphasizes the need to improve the organization of the waiting list for transplantation and to optimize organ availability for patients with and without HCC. Current progress in innovations to expand the donor pool includes the implementation of living donor LT and the use of grafts from extended donors. By expanding selection criteria, an increased number of patients are eligible for transplantation, which necessitates criteria to prevent futile transplantations. Thus, the selection criteria for LT have evolved to include not only tumor characteristics but biomarkers as well. Enhancing our understanding of HCC tumor biology through the analysis of subtypes and molecular genetics holds significant promise in advancing the personalized approach for patients. In this review, the effect of waiting time duration on outcome in patients with HCC enlisted for LT is discussed.
Collapse
Affiliation(s)
- Pam Elisabeth van der Meeren
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Roeland Frederik de Wilde
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Dave Sprengers
- Department of Gastroenterology & Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jan Nicolaas Maria IJzermans
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| |
Collapse
|
|
14
|
Liang B, Huang T, Kuang SL, Xie GY, Liu TQ, Chen YY. Surgery after combination therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody in sarcomatoid hepatocellular carcinoma: case report and literature review. Front Oncol 2023; 13:1212013. [PMID: 37869099 PMCID: PMC10585252 DOI: 10.3389/fonc.2023.1212013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
Introduction Although surgery is the preferred treatment for sarcomatoid hepatocellular carcinoma (SHC), the prognosis remains considerably poor due to early postoperative recurrence and metastasis. Reports on surgery after combined treatment with a tyrosine kinase inhibitor and anti-programmed cell death (PD)-1 antibody are unavailable. Case presentation A 69-year-old male patient with SHC was admitted to our hospital for treatment of a liver tumor that was detected on ultrasonography. Abdominal computed tomography with triple-phase enhancement revealed a lesion in the right hepatic lobe that measured 86.0 mm × 75.0 mm × 71.0 mm. Biopsy revealed a pathological diagnosis of liver sarcoma or sarcomatoid carcinoma. The patient subsequently received transcatheter arterial chemo-embolization, as he did not consent to surgery. More than two months later, he received a combination of lenvatinib with camrelizumab, as computed tomography showed an increase in the lesion size (to 123.0 mm × 90.0 mm × 80.0 mm) and lateral growth posterior to the upper pole of the right kidney. Liver resection was performed after 6 months of systemic therapy; pathological examination confirmed a diagnosis of SHC and showed extensive necrosis of tumor cells. Combined treatment with lenvatinib and camrelizumab was continued for 6 months after surgery. The patient has survived for over 24 months after initial diagnosis and is currently tumor-free. Conclusion Combined systemic therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody may represent a feasible treatment strategy for improving resectability in cases of unresectable SHC. The outcomes with this combination may also be explored in cases of resectable SHC that have a high-risk of recurrence; this may improve the therapeutic effect.
Collapse
Affiliation(s)
- Bin Liang
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Tao Huang
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Shao-Lei Kuang
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Guang-Yuan Xie
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Tian-Qi Liu
- Department of General Surgery, the Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yuan-Yuan Chen
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| |
Collapse
|
|
15
|
He G, Huang W, Zhou Z, Wu H, Tian Q, Tan L, Li X. Dynamic contrast-enhanced CT and clinical features of sarcomatoid hepatocellular carcinoma. Abdom Radiol (NY) 2023; 48:3091-3100. [PMID: 37428205 PMCID: PMC10480274 DOI: 10.1007/s00261-023-03983-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 06/09/2023] [Accepted: 06/12/2023] [Indexed: 07/11/2023]
Abstract
PURPOSE To investigate the dynamic contrast-enhanced computed tomography (CECT) features and clinical characteristics of sarcomatoid hepatocellular carcinoma (S-HCC). METHODS We retrospectively reviewed the CECT data and clinical findings of 13 patients (11 male and 2 female, with an average age of 58.6 ± 11.2 years) with pathologically proven S-HCC, including 9 patients with surgical resection and 4 patients with biopsy examination. All patients underwent CECT scans. Two radiologists reviewed and evaluated general features, CECT features and extratumoral features of each lesions based on a consensus. RESULTS Among the thirteen tumors, a mean size of 66.7 mm was observed, ranging in diameter from 30 to 146 mm. Seven of thirteen patients had hepatitis B virus (HBV) infection and an elevation of alpha-fetoprotein (AFP) level. Most of cases located in the right lobe of liver (84.6%, 11/13). Nine of thirteen tumors showed lobulated or wavy contours and infiltrative morphology, while eight tumors presented with unclear margin. The tumor textures were mainly heterogeneous for ischemia or necrosis, with solid components dominantly in all cases. Eight of thirteen tumors exhibited "slow-in and and slow-out" dynamic enhancement pattern in CECT, with a enhancement peak in the portal venous phase. Portal vein or hepatic thrombus, adjacent organs invasion and lymph node metastasis were observed in two patients, respectively. Four of thirteen lesions occurred intrahepatic metastasis and hepatic surface retraction respectively. CONCLUSION S-HCC gengerally seen in elderly male with HBV infection and elevated AFP level. The CT manifestations including: large diameter, frequently hepatic right lobe involvement, lobular or wavy contours, ill-defined margins, infiltrative morphology, obvious heterogeneity and dynamic enhancement pattern of "slow-in and and slow-out" , contributed to the diagnosis of S-HCC. These tumors usually occurred hepatic surface retraction and intrahepatic metastasis.
Collapse
Affiliation(s)
- Guangming He
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No.250, Changgang East Road, Haizhu District, Guangzhou, 510399 Guangdong China
| | - Weiqing Huang
- Guangzhou Medical University, Guangzhou, 511495 Guangdong China
| | - Zhimei Zhou
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No.250, Changgang East Road, Haizhu District, Guangzhou, 510399 Guangdong China
| | - Hui Wu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No.250, Changgang East Road, Haizhu District, Guangzhou, 510399 Guangdong China
| | - Qin Tian
- Department of Pathology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510399 Guangdong China
| | - Lilian Tan
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No.250, Changgang East Road, Haizhu District, Guangzhou, 510399 Guangdong China
| | - Xi Li
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No.250, Changgang East Road, Haizhu District, Guangzhou, 510399 Guangdong China
| |
Collapse
|
|
16
|
Gabbia D, De Martin S. Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma. Int J Mol Sci 2023; 24:ijms24043441. [PMID: 36834851 PMCID: PMC9960420 DOI: 10.3390/ijms24043441] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/03/2023] [Accepted: 02/05/2023] [Indexed: 02/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the primary hepatic malignancy, represents the second-highest cause of cancer-related death worldwide. Many efforts have been devoted to finding novel biomarkers for predicting both patients' survival and the outcome of pharmacological treatments, with a particular focus on immunotherapy. In this regard, recent studies have focused on unravelling the role of tumor mutational burden (TMB), i.e., the total number of mutations per coding area of a tumor genome, to ascertain whether it can be considered a reliable biomarker to be used either for the stratification of HCC patients in subgroups with different responsiveness to immunotherapy, or for the prediction of disease progression, particularly in relation to the different HCC etiologies. In this review, we summarize the recent advances on the study of TMB and TMB-related biomarkers in the HCC landscape, focusing on their feasibility as guides for therapy decisions and/or predictors of clinical outcome.
Collapse
|
|
17
|
Jia B, Xia P, Dong J, Feng W, Wang W, Liu E, Jiang G, Qin Y. Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients. Front Oncol 2023; 12:1086908. [PMID: 36741696 PMCID: PMC9891294 DOI: 10.3389/fonc.2022.1086908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 12/20/2022] [Indexed: 01/19/2023] Open
Abstract
Background Sarcomatoid hepatocellular carcinoma (SHC) is a rare epithelial malignancy with high invasiveness and poor prognosis. However, the molecular characteristics and main driver genes for SHC have not been determined. The aim of this study is to explore the potentially actionable mutations of driver genes, which may provide more therapeutic options for SHC. Methods In this study, DNA extraction and library preparation were performed using tumor tissues from 28 SHC patients. Then we used Miseq platform (Illumina) to sequence the target-enriched library, and we aligned and processed the sequencing data. The gene groups were tested for SNVs/Indels/CNVs. Tumor mutation burden (TMB) was assessed by the 425-cancer-relevant gene panel. Multivariate analysis of COX's model was used for survival analysis (OS) of patients' clinical characteristics. Result The median overall survival (OS) of the patients was only 4.4 months. TP53, TERT, and KRAS were the top three frequently mutated genes, with frequencies of 89.3%, 64.3%, and 21.4%, respectively. A considerable number of patients carried mutations in genes involved in the TP53 pathway (96%) and DNA Damage Repair (DDR) pathway (21%). Multiple potentially actionable mutations, such as NTRK1 fusions and BRCA1/2 mutations, were identified in SHCs. Conclusions This study shows a landscape of gene mutations in SHC. SHC has high mutation rates in TP53 pathway and DDR pathway. The potentially actionable mutations of driver genes may provide more therapeutic options for SHC. Survival analysis found that age, smoking, drinking, and tumor diameter may be independent prognostic predictors of SHC.
Collapse
Affiliation(s)
- Bin Jia
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Peiyi Xia
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Junqiang Dong
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Wenhao Feng
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Wenjia Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Enjie Liu
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Guozhong Jiang
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China,*Correspondence: Guozhong Jiang, ; Yanru Qin,
| | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China,*Correspondence: Guozhong Jiang, ; Yanru Qin,
| |
Collapse
|
|
18
|
Yang T, Wei H, Wu Y, Qin Y, Chen J, Jiang H, Song B. Predicting histologic differentiation of solitary hepatocellular carcinoma up to 5 cm on gadoxetate disodium-enhanced MRI. Insights Imaging 2023; 14:3. [PMID: 36617583 PMCID: PMC9826771 DOI: 10.1186/s13244-022-01354-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 12/13/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND To establish a preoperative score based on gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators for predicting histologic differentiation of solitary HCC up to 5 cm. METHODS From July 2015 to January 2022, consecutive patients with surgically proven solitary HCC measuring ≤ 5 cm at preoperative EOB-MRI were retrospectively enrolled. All MR images were independently evaluated by two radiologists who were blinded to all clinical and pathologic information. Univariate and multivariate logistic regression analyses were performed to identify significant clinicoradiological features associated with poorly differentiated (PD) HCC, which were then incorporated into the predictive score. The predictive score was validated in an independent validation set by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. RESULTS A total of 182 patients were included, 42 (23%) with PD HCC. According to the multivariate analysis, marked hepatobiliary phase hypointensity (odds ratio [OR], 9.98), LR-M category (OR, 5.60), and serum alpha-fetoprotein (AFP) level > 400 ng/mL (OR, 3.58) were incorporated into the predictive model; the predictive score achieved an AUC of 0.802 and 0.830 on the training and validation sets, respectively. The sensitivity, specificity, and accuracy of the predictive score were 66.7%, 85.7%, and 81.3%, respectively, on the training set and 66.7%, 81.0%, and 77.8%, respectively, on the validation set. CONCLUSION The proposed score integrating two EOB-MRI features and AFP level can accurately predict PD HCC in the preoperative setting.
Collapse
Affiliation(s)
- Ting Yang
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Hong Wei
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Yuanan Wu
- grid.54549.390000 0004 0369 4060Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, 610000 Sichuan China
| | - Yun Qin
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Jie Chen
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Hanyu Jiang
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Bin Song
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China ,Department of Radiology, Sanya People’s Hospital, Sanya, Hainan China
| |
Collapse
|
|
19
|
Ma S, Zhang D, Zhao G, Ding S, Wu Q, Zhang X, Lu Z. Gastric infiltration of hepatic sarcomatoid carcinoma: A case report and literature review. Front Surg 2023; 9:1031284. [PMID: 36684166 PMCID: PMC9852497 DOI: 10.3389/fsurg.2022.1031284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 10/21/2022] [Indexed: 01/09/2023] Open
Abstract
Background Hepatic sarcomatoid carcinoma (HSC) is an extremely rare malignant tumor typically observed in clinical settings. HSC occurrence is predominantly noted in the right lobe and rarely in the left lobe of the liver. This report presents a case of sarcomatoid carcinoma that occurred in the left outer lobe of the liver, which was accompanied by gastrointestinal stromal tumors (GSTs) in the greater curvature of the stomach. In addition, the patient showed late-stage recurrence of HSC in gastric tissues. Case presentation A 63-year-old man was concomitantly diagnosed with HSC and GST. The main clinical manifestation was fever. Abdominal computer tomography (CT) and ultrasound-guided percutaneous liver biopsy at the local hospital revealed the presence of malignant hepatic tumors. The patient approached our hospital for further treatment. The subsequent electronic gastroscopy showed multiple submucosal tumors (SMT) in the stomach. Owing to the absence of multiple metastases in other regions of the body, we performed left hepatic lobe resection with gastric partial resection. The postoperative pathological analysis confirmed the presence of HSC and GST. The patient reported feeling well 1 month after the surgery, and no obvious space-occupying lesions in other areas were noted via imaging examinations. However, 3 months later, the patient presented with pain in the upper left abdomen, and examination revealed cancer recurrence in the stomach. The surgery was repeated, and the patient recovered favorably after the procedure. Unfortunately, the patient died owing to multiple metastatic diseases 4 months after the second surgical procedure. Conclusion HSC shows no characteristic clinical manifestations and is highly malignant. Surgical intervention is the first treatment of choice for patients with HSC. In cases of sarcomatoid cancer occurring in the left lobe of the liver, it is imperative to exercise strict vigilance against the tumor's invasion of the stomach tissue. This is particularly important when the tumor breaks through the capsule of the liver.
Collapse
Affiliation(s)
- Shuoshuo Ma
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Dengyong Zhang
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Guanru Zhao
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Sheng Ding
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Qiong Wu
- Department of Pathology, Hospital of Bengbu Medical College, Bengbu, China
| | - Xueli Zhang
- Department of Radiology, Hospital of Bengbu Medical College, Bengbu, China
| | - Zheng Lu
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China,Correspondence: Zheng Lu
| |
Collapse
|
|
20
|
Yoshuantari N, Jeng YM, Liau JY, Lee CH, Tsai JH. Hepatic Sarcomatoid Carcinoma Is an Aggressive Hepatic Neoplasm Sharing Common Molecular Features With Its Conventional Carcinomatous Counterparts. Mod Pathol 2023; 36:100042. [PMID: 36788061 DOI: 10.1016/j.modpat.2022.100042] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/11/2022] [Accepted: 10/11/2022] [Indexed: 01/19/2023]
Abstract
Hepatic sarcomatoid carcinoma is a rare hepatic tumor with an aggressive clinical behavior and dismal outcome. However, the molecular pathogenesis is incompletely defined. In this study, we analyzed 59 hepatic sarcomatoid carcinomas using targeted next-generation sequencing and immunohistochemistry. A panel of 14 genes commonly mutated in primary liver carcinomas was examined. PD-L1 and loss of expression for switch/sucrose nonfermenting complexes, including BAP1, ARID1A, ARID2, and PBRM1, were detected by immunohistochemistry. The 59 hepatic sarcomatoid carcinomas encompass various carcinomatous subtypes and tumors with complete sarcomatoid transformation. Mutations in TP53 and promoter of TERT (pTERT) were frequently identified in sarcomatoid hepatocellular carcinoma, sarcomatoid combined hepatocellular cholangiocarcinoma, and hepatic sarcomatoid carcinomas with complete sarcomatoid transformation but rarely in sarcomatoid cholangiocarcinoma. Alterations involving switch/sucrose nonfermenting complexes were uncommon in hepatic sarcomatoid carcinoma (n = 2). PD-L1 expressed in tumor-associated immune cells in 67% of the tumors and in tumor cells in 33% of the tumors. A multivariate survival analysis indicated that PD-L1 expression in immune cells served as an independent favorable predictive factor of patient survival (P = .036). In conclusion, hepatic sarcomatoid carcinoma displays molecular similarity with its conventional carcinomatous counterparts. This finding suggests persistent genetic characteristics during sarcomatous evolution. PD-L1 expression in immune cells is a favorable prognostic factor for patient outcomes and may be a potential biomarker for immunotherapeutic treatment.
Collapse
Affiliation(s)
- Naomi Yoshuantari
- Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia
| | - Yung-Ming Jeng
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jau-Yu Liau
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chia-Hsiang Lee
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Huei Tsai
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
| |
Collapse
|
|
21
|
Fencer MG, Davis CH, Liu J, Galan MA, Spencer KR. Disease Control Achieved Using Atezolizumab + Bevacizumab in a Patient With Sarcomatoid Hepatocellular Carcinoma (SHCC), a Rare Variant Excluded From the IMbrave150 Trial. J Investig Med High Impact Case Rep 2022; 10:23247096221129470. [PMID: 36541195 PMCID: PMC9791267 DOI: 10.1177/23247096221129470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Sarcomatoid hepatocellular carcinoma (SHCC) is a rare variant of liver cancer that lacks treatment options. The IMbrave trail demonstrated the efficacy of atezolizumab and bevacizumab (A + B) in patients with unresectable hepatocellular carcinoma but excluded patients with sarcomatoid variants. Herein, we describe a case of disease control achieved using the IMbrave regimen in a patient with sarcomatoid hepatocellular carcinoma.
Collapse
Affiliation(s)
- Maria G. Fencer
- Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ, USA,Rutgers New Jersey Medical School, Newark, USA
| | - Catherine H. Davis
- Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ, USA,Rutgers Cancer Institute of New Jersey, New Brunswick, USA
| | - Jieqi Liu
- Rutgers Cancer Institute of New Jersey, New Brunswick, USA
| | | | - Kristen R. Spencer
- Rutgers Cancer Institute of New Jersey, New Brunswick, USA,Kristen R. Spencer, DO, MPH, Division of Medical Oncology, New York University, 160 E 34th St, New York NY 10016, USA.
| |
Collapse
|
|
22
|
Sweed D, Sweed E, Moaz I, Mosbeh A, Fayed Y, Elhamed SMA, Sweed E, Macshut M, Abdelsattar S, Kilany S, Saied SA, Badr R, Abdallah MS, Ehsan N. The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt. World J Surg Oncol 2022; 20:298. [PMID: 36117166 PMCID: PMC9484175 DOI: 10.1186/s12957-022-02764-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/06/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).
Collapse
Affiliation(s)
- Dina Sweed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Enas Sweed
- Radiology Department, Faculty of Medicine, Benha University, Benha, Egypt
| | - Inas Moaz
- Epidemiology, and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Asmaa Mosbeh
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Yahya Fayed
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara Mohamed Abd Elhamed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Eman Sweed
- Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud Macshut
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Kilany
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara A. Saied
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Reda Badr
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud S. Abdallah
- Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufia Egypt
| | - Nermine Ehsan
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| |
Collapse
|
|
23
|
Ma S, Li C, Ma Y, Wang X, Zhang D, Lu Z. A retrospective study on the clinical and pathological features of hepatic sarcomatoid carcinoma: Fourteen cases of a rare tumor. Medicine (Baltimore) 2022; 101:e30005. [PMID: 35945746 PMCID: PMC9351887 DOI: 10.1097/md.0000000000030005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Hepatic sarcomatoid carcinoma is a rare liver malignancy with atypical clinical symptoms and a high degree of malignancy. To improve the understanding of this disease, we collected the clinical and pathological data of 14 patients with hepatic sarcomatoid carcinoma admitted to the First Affiliated Hospital and Second Affiliated Hospital of Bengbu Medical College from 2011 to 2021 and reviewed the relevant literature. The clinical and pathological data of 14 patients with hepatic sarcomatoid carcinoma were collected from the electronic medical record system of the 2 hospitals. All clinical data were independently reviewed by 2 clinicians, and all pathological data were independently reviewed by 2 pathologists. At the same time, we reviewed the related literature on hepatic sarcomatoid carcinoma in Pubmed and CNKI. This group of 14 patients, 10 males and 4 females, aged 50-77 years. The main symptoms of the patients were abdominal pain, bloating, anorexia, fatigue or weight loss in the upper abdomen, and 3 patients were asymptomatic. On imaging, hepatic sarcomatoid carcinoma manifests as heterogeneous mass with irregular shape and unclear boundary, and computed tomography (CT)/magnetic resonance imaging (MRI) enhanced scan shows progressive or persistent heterogeneous enhancement, marginal enhancement or annular enhancement, and central necrosis. The pathological features of hepatic sarcomatoid carcinoma are the proliferation of spindle cells and pleomorphic cells, which alternate with acinar cells. Hepatic sarcomatoid carcinoma is more common in middle-aged and elderly patients, especially men, and has no characteristic clinical manifestations. Imaging examination and B-ultrasound-guided liver biopsy + immunohistochemistry can help diagnose. Radical surgery is the preferred method for hepatic sarcomatoid carcinoma, and postoperative adjuvant chemotherapy is expected to prolong patient survival.
Collapse
Affiliation(s)
- Shuoshuo Ma
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical Collage
| | - Chunshuang Li
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College
| | - Yang Ma
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical Collage
| | - Xiaolei Wang
- Department of Imaging, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Dengyong Zhang
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical Collage
| | - Zheng Lu
- Department of General Surgery, The First Affiliated Hospital of Bengbu Medical Collage
| |
Collapse
|
|
24
|
MRI features of histologic subtypes of hepatocellular carcinoma: correlation with histologic, genetic, and molecular biologic classification. Eur Radiol 2022; 32:5119-5133. [PMID: 35258675 DOI: 10.1007/s00330-022-08643-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 01/31/2022] [Accepted: 02/11/2022] [Indexed: 02/07/2023]
Abstract
HCC is a heterogeneous group of tumors in terms of histology, genetic aberration, and protein expression. Advancements in imaging techniques have allowed imaging diagnosis to become a critical part of managing HCC in the clinical setting, even without pathologic diagnosis. With the identification of many HCC subtypes, there is increasing correlative evidence between imaging phenotypes and histologic, molecular, and genetic characteristics of various HCC subtypes. In this review, current knowledge of histologic heterogeneity of HCC correlated to features on gadolinium-enhanced dynamic liver MRI will be discussed. In addition, HCC subtype classification according to transcriptomic profiles will be outlined with descriptions of histologic, genetic, and molecular characteristics of some relatively well-established morphologic subtypes, namely the low proliferation class (steatohepatitic HCC and CTNNB1-mutated HCC) and the high proliferation class (macrotrabecular-massive HCC (MTM-HCC), scirrhous HCC, and CK19-positive HCC). Characteristics of sarcomatoid HCC and fibrolamellar HCC will also be discussed. Further research on radiological characteristics of HCC subtypes may ultimately enable non-invasive diagnosis and serve as a biomarker in predicting prognosis, molecular characteristics, and therapeutic response. In the era of precision medicine, a multidisciplinary effort to develop an integrated radiologic and clinical diagnostic system of various HCC subtypes is necessary. KEY POINTS: • HCC is a heterogeneous group of tumors in terms of histology, genetic aberration, and protein expression, which can be divided into many subtypes according to transcriptome profiles. • There is increasing evidence of a correlation between imaging phenotypes and histologic, genetic, and molecular biologic characteristics of various HCC subtypes. • Imaging characteristics may ultimately enable non-invasive diagnosis and subtype characterization, serving as a biomarker for predicting prognosis, molecular characteristics, and therapeutic response.
Collapse
|
|
25
|
Queiroz MM, Munhoz RR, Masotti C, Souza LM, Lima LGCA, Asprino PF, Begnami MDFS, Camargo AA, Bettoni F. Durable Response to Nivolumab in a Patient With Hepatic Sarcomatoid Carcinoma: Evolutive Characterization of Genomic and Immunohistochemical PD-L1 Expression Findings. JCO Precis Oncol 2022; 6:e2200163. [PMID: 36044716 PMCID: PMC9489170 DOI: 10.1200/po.22.00163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
| | | | - Cibele Masotti
- Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, SP, Brazil
| | - Larissa M Souza
- Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, SP, Brazil
| | - Luiz G C A Lima
- Department of Pathology, Hospital Sírio-Libanês, São Paulo, SP, Brazil
| | - Paula F Asprino
- Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, SP, Brazil
| | | | - Anamaria A Camargo
- Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, SP, Brazil
| | - Fabiana Bettoni
- Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, SP, Brazil
| |
Collapse
|
|
26
|
Lv TR, Hu HJ, Regmi P, Liu F, Li FY. Sarcomatoid hepatocellular carcinoma versus conventional hepatocellular carcinoma: a systematic review and meta-analysis. J Cancer Res Clin Oncol 2022; 148:1685-1696. [PMID: 35201426 DOI: 10.1007/s00432-022-03949-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 02/06/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Sarcomatoid hepatocellular carcinoma (SHCC) is a rare subtype of primary liver malignancies and is still ill-defined and poorly understood. Therefore, our study was performed to have a comprehensive evaluation SHCC versus conventional hepatocellular carcinoma (HCC). METHODS A thorough database searching was performed in PubMed, EMBASE and the Cochrane Library. RevMan5.3 and Stata 13.0 software were used for statistical analyses. The primary endpoint of our analysis is the long-term survival and the secondary endpoint is clinical and pathological features. RESULTS Four studies with a relative large cohort were finally identified. Compared with patients with pure HCC, patients with SHCC had a significantly worse overall survival (P < 0.00001) and disease-free survival (P < 0.0001). Moreover, a larger tumor size (P = 0.003), a higher incidence of node metastasis (P < 0.00001) and a higher proportion of advanced lesions (P = 0.04) were more frequently detected in patients with SHCC. Higher levels of serum ALT (P = 0.02) and TB (P = 0.005) were detected in patients with HCC rather than SHCC, while serum ALB (P = 0.02) level was relatively higher in patients with SHCC. For other measured outcomes, including concurrent viral hepatitis, liver cirrhosis, liver storage (Child A/B), multifocal tumors, vascular invasion and preoperative AFP level, the results showed no significant difference (P > 0.05). CONCLUSION SHCC has a worse prognosis and exhibits more aggressively than conventional HCC. Future large well-designed studies are demanded for further validation.
Collapse
Affiliation(s)
- Tian-Run Lv
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Parbatraj Regmi
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| |
Collapse
|
|
27
|
Yang T, Zou MH, Zou Q, Jiao J, Zhang Y. 18F-FDG PET/CT Imaging in Sarcomatoid Hepatocellular Carcinoma. Clin Nucl Med 2022; 47:427-429. [PMID: 35293354 DOI: 10.1097/rlu.0000000000004121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Sarcomatoid hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma. We present a 53-year-old man with a hepatic IV/VIII segment neoplasm whose tumor markers were all in the reference range. The neoplasm presented intense uptake of 18F-FDG and was confirmed as sarcomatoid hepatocellular carcinoma by immunohistochemistry. After 6 cycles of PD-1 treatment, no recurrence or metastasis was found by follow-up CT over 2 years. Thus, we reported a case of sarcomatoid hepatocellular carcinoma with complete remission to PD-1 treatment and provided some help for the diagnosis and treatment of sarcomatoid hepatocellular carcinoma.
Collapse
Affiliation(s)
- Ting Yang
- From the Departments of Nuclear Medicine
| | - Min-Hong Zou
- Ultrasonic Diagnosis, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Qiong Zou
- From the Departments of Nuclear Medicine
| | - Ju Jiao
- From the Departments of Nuclear Medicine
| | - Yong Zhang
- From the Departments of Nuclear Medicine
| |
Collapse
|
|
28
|
Chen X, Lu Y, Shi X, Han G, Zhang L, Ni C, Zhao J, Gao Y, Wang X. Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma. Front Oncol 2022; 12:864106. [PMID: 35463333 PMCID: PMC9026181 DOI: 10.3389/fonc.2022.864106] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/14/2022] [Indexed: 12/14/2022] Open
Abstract
BackgroundHepatocellular carcinoma (HCC) is a highly heterogeneous tumor with several rare pathological subtypes and which is still poorly understood. This study aimed to describe the epidemiological and clinical spectrum of five rare HCC subtypes and develop a competing risk nomogram for cancer-specific survival prediction.MethodsThe study cohort was recruited from the Surveillance, Epidemiology, and End Results database. The clinicopathological data of 50,218 patients histologically diagnosed with classic HCC and five rare subtypes (ICD-O-3 Histology Code = 8170/3-8175/3) between 2004 and 2018 were reviewed. The annual percent change (APC) was calculated utilizing Joinpoint regression. The nomogram was developed based on multivariable competing risk survival analyses. Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve were obtained to evaluate the prognostic performance. A decision curve analysis was introduced to examine the clinical value of the models.ResultsDespite scirrhous carcinoma, which showed a decreasing trend (APC = -6.8%, P = 0.025), the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality was plateau in all subtypes during the period. Clear cell carcinoma is the most common subtype (n = 551, 1.1%), followed by subtypes of fibrolamellar (n = 241, 0.5%), scirrhous (n = 82, 0.2%), spindle cell (n = 61, 0.1%), and pleomorphic (n = 17, ~0%). The patients with fibrolamellar carcinoma were younger and more likely to have a non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro-clinical characteristics and outcomes as the classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with a larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were confirmed as the independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice.ConclusionThe rare subtypes had unique clinicopathological features and biological behaviors compared with the classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could predict the prognoses with good performance, which is meaningful to individualized management.
Collapse
Affiliation(s)
- Xiaoyuan Chen
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
- School of Medicine, Southeast University, Nanjing, China
| | - Yiwei Lu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
| | - Xiaoli Shi
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
- School of Medicine, Southeast University, Nanjing, China
| | - Guoyong Han
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
| | - Long Zhang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
| | - Chuangye Ni
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
| | - Jie Zhao
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Yun Gao
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
- *Correspondence: Xuehao Wang, ; Yun Gao,
| | - Xuehao Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China
- School of Medicine, Southeast University, Nanjing, China
- *Correspondence: Xuehao Wang, ; Yun Gao,
| |
Collapse
|
|
29
|
Zhang X, Wang X, Jia L, Yang Y, Yang F, Xiao S. CtBP1 Mediates Hypoxia-Induced Sarcomatoid Transformation in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:57-67. [PMID: 35186805 PMCID: PMC8847960 DOI: 10.2147/jhc.s340471] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 02/02/2022] [Indexed: 11/23/2022] Open
Abstract
Background Sarcomatoid hepatocellular carcinoma (sHCC), a highly aggressive subtype of hepatocellular carcinoma (HCC), mostly transforms from classical hepatocellular carcinoma (cHCC). The study intended to explore the role of C-terminal binding protein 1 (CtBP1) in sarcomatoid transformation of hepatocellular carcinoma. Methods Western blotting and/or immunohistochemistry were used to confirm the expression of CtBP1 and other proteins in HCC cells, xenografts and clinical tissue samples. CtBP1 shRNA-expressing lentivirus was used to infect HepG2 cells to construct CtBP1 knockdown cells. Cell migration was determined by scratch wound assays and Transwell assays. Immunofluorescence was used to label the a-tubulin cytoskeleton to evaluate cell morphology. HepG2 cells were inoculated subcutaneously in nude mice to construct xenografts and beneath the liver capsule to evaluate in vivo metastasis. Results Compared to that in the cHCC area, CtBP1 expression was significantly upregulated in the sHCC area, as shown by immunohistochemistry. HE staining showed that cells in the sHCC area were spindle-shaped, while those in the cHCC area were polygonal. Immunohistochemically, the epithelial markers pancytokeratin (CK) and E-cadherin were partially or completely lost, while the expression of the mesenchymal marker vimentin was upregulated in the sHCC area. Moreover, HepG2, an HCC cell line with high expression of CtBP1, autonomously underwent sarcomatoid transformation, showing a sarcomatoid morphology and phenotype. HIF1a expression was upregulated in epithelial cells adjacent to the sHCC area. Hypoxia upregulated CtBP1 protein expression and induced an EMT phenotype with increased migration and a spindle-shaped morphology in HepG2 cells. Knockdown of CtBP1 partially reversed the EMT phenotype induced by hypoxia. Silencing CtBP1 completely blocked the sarcomatoid transformation of subcutaneous xenografts and decreased lung metastasis in subcapsular xenografts of the liver in nude mice. Conclusion CtBP1 plays a key role in hypoxia-induced EMT and sarcomatoid transformation in HCC and could be a candidate target for the management of sHCC.
Collapse
Affiliation(s)
- Xiaoling Zhang
- Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, People’s Republic of China
- Key Laboratory of Tumor Immunology and Microenvironmental Regulation of Guangxi, Guilin Medical University, Guilin, People’s Republic of China
- Xiaoling Zhang, Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, No. 1, Zhiyuan Road, Guilin, Guangxi Province, 541100, People’s Republic of China, Email
| | - Xiaoyu Wang
- Department of Pathology, the Second Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China
| | - Liting Jia
- Department of Pathology, Affiliated Hospital of Hebei Engineering University, Handan, People’s Republic of China
| | - Yang Yang
- Department of Pathology, General Hospital of Central Theater Command, Wuhan, People’s Republic of China
| | - Fan Yang
- Department of Pathology, the Second Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China
| | - Shengjun Xiao
- Key Laboratory of Tumor Immunology and Microenvironmental Regulation of Guangxi, Guilin Medical University, Guilin, People’s Republic of China
- Department of Pathology, the Second Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China
- Department of Pathology, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, the Second Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China
- Correspondence: Shengjun Xiao, Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, No. 212, Renmin Road, Guilin, Guangxi Province, 541199, People’s Republic of China, Email
| |
Collapse
|
|
30
|
Sadiq AM, Mjemmas MG, Sadiq AM, Nkya GZ. Sarcomatoid hepatocellular carcinoma in a young African female. SAGE Open Med Case Rep 2021; 9:2050313X211052452. [PMID: 34646567 PMCID: PMC8504208 DOI: 10.1177/2050313x211052452] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 09/23/2021] [Indexed: 12/24/2022] Open
Abstract
Sarcomatoid hepatocellular carcinoma is a rare primary malignant liver cancer. The pathogenesis is unclear; however, the risk factors may be similar to that of conventional hepatocellular carcinoma. We present an 18-year-old female who was admitted due to generalized tonic-clonic convulsions. On examination, we palpated a large non-tender mass in the right upper quadrant. An abdominal computed tomography identified it as hepatocellular carcinoma, and spindle-shaped cells were seen on histopathology. She was counseled on her prognosis but opted for local herbal medications rather than chemotherapy, but unfortunately passed away. We present a rare subtype of hepatocellular carcinoma in a young female which is commonly seen in males above the age of 50 years, and despite its grade and stage, overall survival is poor.
Collapse
Affiliation(s)
- Abid M Sadiq
- Department of Internal Medicine, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.,Kilimanjaro Christian Medical University College, Moshi, Tanzania
| | - Minael G Mjemmas
- Department of Internal Medicine, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - Adnan M Sadiq
- Kilimanjaro Christian Medical University College, Moshi, Tanzania.,Department of Radiology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - Gilbert Z Nkya
- Kilimanjaro Christian Medical University College, Moshi, Tanzania.,Department of Pathology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| |
Collapse
|
|
31
|
Zhang C, Feng S, Tu Z, Sun J, Rui T, Zhang X, Huang H, Ling Q, Zheng S. Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome. Cancer Med 2021; 10:6227-6238. [PMID: 34331411 PMCID: PMC8446410 DOI: 10.1002/cam4.4162] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/12/2021] [Accepted: 06/12/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Sarcomatoid hepatocellular carcinoma (HCC) is a rare and highly lethal histological subtype of HCC, with completely unknown genetic etiology and therapeutic targets. METHODS We included 16 patients with sarcomatoid HCC receiving radical resection among 6731 cases of pathological confirmed HCC in year 2008 to 2018 in our hospital. We compared the clinical features, prognosis and cancer genome between 15 sarcomatoid HCC and propensity score-matched 75 non-sarcomatoid HCC patients. The other concurrent case was analyzed using phylogenetic tree to assess the tumor heterogeneity and evolution. RESULTS Sarcomatoid HCC group showed larger tumor size, more advanced differentiation grade, lower tumor free survival (p = 0.038) and overall survival (p = 0.001), and sarcomatoid type was an independent risk factor for patient death. Integrating sarcomatoid subtype into AJCC staging could increase the diagnostic curve in predicting patient survival. The cancer genome spectrum showed sarcomatoid HCC group had significant higher mutation rates in CDKN2A, EPHA5, FANCM and MAP3K1. Mutations in CDKN2A significantly reduced tumor-free and overall survival in sarcomatoid HCC patients. Moreover, 46.6% sarcomatoid HCC patients had druggable mutations in cell cycle pathway genes, which were targeted by Abemaciclib, et al. We also found sarcomatoid and non-sarcomatoid lesions might originate from a common progenitor but progress differently. CONCLUSION Our cancer genome analysis showed a specific genomic profile of sarcomatoid HCC, which were characterized by a high mutation rate in cell cycle genes particularly CDKN2A. The results indicate CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and may help for therapeutic decision making.
Collapse
MESH Headings
- Aged
- Aminopyridines/therapeutic use
- Benzimidazoles/therapeutic use
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/therapy
- Chemotherapy, Adjuvant
- Cyclin-Dependent Kinase Inhibitor p16/genetics
- DNA Helicases/genetics
- Disease-Free Survival
- Female
- Follow-Up Studies
- Hepatectomy
- Humans
- Liver/pathology
- Liver/surgery
- Liver Neoplasms/diagnosis
- Liver Neoplasms/genetics
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- MAP Kinase Kinase Kinase 1/genetics
- Male
- Middle Aged
- Mutation Rate
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/genetics
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/prevention & control
- Prognosis
- Receptor, EphA5/genetics
- Risk Factors
- Tumor Burden
Collapse
Affiliation(s)
- Cheng Zhang
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Shi Feng
- Department of Pathologythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Zhenhua Tu
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Jingqi Sun
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Tao Rui
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Xueyou Zhang
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Haitao Huang
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Qi Ling
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- Key Laboratory of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
| | - Shusen Zheng
- Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- Key Laboratory of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
| |
Collapse
|
|
32
|
Rare variants of primary liver cancer: Fibrolamellar, combined, and sarcomatoid hepatocellular carcinomas. Eur J Med Genet 2021; 64:104313. [PMID: 34418585 DOI: 10.1016/j.ejmg.2021.104313] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 06/21/2021] [Accepted: 07/22/2021] [Indexed: 01/07/2023]
Abstract
Hepatocellular carcinoma (HCC) constitutes 80% of all primary liver cancers. Based on key developments in the understanding of its carcinogenesis and the advancement of treatment options, detailed algorithms and practice guidelines have been published to guide the clinical management of HCC. Furthermore, several subclasses of HCC have been described based on molecular profiles and linked to pathological characteristics, clinical features, and disease aggressiveness. Most recently, the combination of the checkpoint inhibitor atezolizumab plus bevacizumab has significantly increased treatment response in the first line systemic treatment of HCC. Unfortunately, rare HCC variants, in particular fibrolamellar liver cancer (FLC), combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA), and sarcomatoid hepatocellular carcinoma (sHCC), were excluded from phase III studies. Therefore, data for decision-making and treatment allocation for these distinct entities, representing 1-5% of all primary liver cancers, is scarce. Moreover, most of the knowledge available for these rare HCC variants is based on registry data and retrospective studies. In this position paper, we briefly summarize the current clinical knowledge regarding FLC, cHCC-CCA, and sHCC. Based on our summary, we propose future clinical research activities within the framework of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
Collapse
|
|
33
|
Zhang H, Chai S, Chen L, Wang Y, Cheng Y, Fang Q, Wu G, Wang X, Liang W, Xiao W. MRI Features of Hepatic Sarcomatoid Carcinoma Different From Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 11:611738. [PMID: 34221954 PMCID: PMC8247642 DOI: 10.3389/fonc.2021.611738] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 05/25/2021] [Indexed: 12/25/2022] Open
Abstract
Introduction Hepatic sarcomatoid carcinoma (HSC) is a rare type of liver cancer with a high malignant grade and poor prognosis. This study compared the clinical characteristics and magnetic resonance imaging (MRI) features of HSCs with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), aiming to identify valuable features for HSC diagnosis. Methods In total, 17 pathologically confirmed HSC cases, 50 HCC cases and 50 common ICC cases were enrolled from two hospitals. The clinical characteristics and MRI features of all cases were summarized and statistically analyzed. Results On the one hand, the incidence rates of elevated carbohydrate antigen (CA) 19-9 and elevated carcinoembryonic antigen (CEA) were significantly higher in the HSC cases than in the HCC cases (29.4% vs. 0%; 17.6% vs. 0%). The HSC enhancement patterns, primarily including progressive enhancement, were also significantly different from HCC cases. The incidence rates of heterogeneous signals on T2-weighted imaging and during the arterial phase were significantly higher in the HSC cases than in the HCC cases (94.1% vs. 66.0%; 100.0% vs. 72.0%). The diameter of HSCs was significantly larger than that in the HCC cases (6.12 cm vs. 4.21 cm), and the incidence rates of adjacent cholangiectasis, intrahepatic metastasis and lymph node enlargement were considerably higher in the HSC cases than in the HCC cases (52.9% vs. 6.0%; 47.1% vs. 12.0%; 41.2% vs. 2.0%). On the other hand, the incidence rate of elevated CA199 was significantly lower in the HSC cases than in the ICC cases (29.4% vs. 60.0%). The incidence rates of intratumoral necrosis and pseudocapsules were significantly higher in the HSC cases than in the HCC cases (35.3% vs. 8.0%; 47.1% vs. 12.0%). However, the incidence rates of target signs were significantly lower in the HSC cases than in the HCC cases (11.8% vs. 42.0%). In addition, there was no significant difference in the enhancement patterns between HSC cases and ICC cases. Conclusions HSCs were frequently seen in elderly men with clinical symptoms and elevated CA199 levels. The MRI features, including large size, obvious heterogeneity, hemorrhage, progressive enhancement, pseudocapsule and lymph node enlargement, contributed to the diagnosis of HSC.
Collapse
Affiliation(s)
- Hongbin Zhang
- Department of Radiology, Yiwu Central Hospital, Yiwu, China
| | - Siyuan Chai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lintao Chen
- Department of Radiology, Yiwu Central Hospital, Yiwu, China
| | - Yubizhuo Wang
- Department of Radiology, Yiwu Central Hospital, Yiwu, China
| | - Yongna Cheng
- Department of Radiology, Yiwu Central Hospital, Yiwu, China
| | - Quan Fang
- Department of Radiology, Yiwu Central Hospital, Yiwu, China
| | - Guosen Wu
- Department of Radiology, Yiwu Central Hospital, Yiwu, China
| | - Xiangming Wang
- Department of Radiology, Yiwu Central Hospital, Yiwu, China
| | - Wenjie Liang
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenbo Xiao
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
34
|
Luo C, Xin H, Yin D, Zhao T, Hu Z, Zhou Z, Sun R, Yao N, Sun Q, Fan J, Huang X, Zhou J, Zhou S. Characterization of immune infiltration in sarcomatoid hepatocellular carcinoma. Aging (Albany NY) 2021; 13:15126-15138. [PMID: 34081621 PMCID: PMC8221324 DOI: 10.18632/aging.203076] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 04/29/2021] [Indexed: 12/11/2022]
Abstract
Sarcomatoid hepatocellular carcinoma (sHCC) is a rare type of liver malignancy. Currently, the tumor immune features of sHCC are poorly understood. We recruited 31 patients with resected sHCC for whom tissue samples and complete clinicopathologic and follow-up data were available. To understand the immune infiltration of sHCC, immunohistochemical staining was performed on the resected sHCC samples to compare the expressions of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), B7-H3, indoleamine 2,3-dioxygenase (IDO), lymphocyte-activation gene 3 (LAG-3), CD8, FOXP3, and CD68 in tumor and peritumoral tissues. Kaplan-Meier and Cox regression analyses were used to assess the predictive value of immune markers. Sarcomatoid components were characterized with significantly higher expression of PD-L1 and B7-H3 in tumor cells than in conventional HCC components, as well as in peritumoral tissue. Additionally, sarcomatoid components had a higher density of FOXP3+ and LAG-3+ cells and a lower density of CD8+ cells than conventional HCC components or peritumoral tissue. Higher expression of PD-L1 in tumor cells significantly correlated with higher densities of CD8+, PD-1+, and LAG-3+ cells. Increased tumor PD-L1 expression and decreased CD8+ T-cell density were associated with poor overall survival (OS) and disease-free survival (DFS) in patients of sHCC. These findings suggest further characterization on relative mechanism of sHCC immune infiltration may identify therapeutic targets for immunotherapy.
Collapse
Affiliation(s)
- Chubin Luo
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Haoyang Xin
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Dan Yin
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Tongyi Zhao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Zhiqiang Hu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Zhengjun Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Rongqi Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Na Yao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Qiman Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Xiaowu Huang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| | - Shaolai Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
| |
Collapse
|
|
35
|
Dian MJ, Li J, Zhang XL, Li ZJ, Zhou Y, Zhou W, Zhong QL, Pang WQ, Lin XL, Liu T, Liu YA, Li YL, Han LX, Zhao WT, Jia JS, Xiao SJ, Xiao D, Xia JW, Hao WC. MST4 negatively regulates the EMT, invasion and metastasis of HCC cells by inactivating PI3K/AKT/Snail1 axis. J Cancer 2021; 12:4463-4477. [PMID: 34149910 PMCID: PMC8210547 DOI: 10.7150/jca.60008] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 05/08/2021] [Indexed: 12/23/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a poor prognosis due to the high incidence of invasion and metastasis-related progression. However, the underlying mechanism remains elusive, and valuable biomarkers for predicting invasion, metastasis, and poor prognosis of HCC patients are still lacking. Methods: Immunohistochemistry (IHC) was performed on HCC tissues (n = 325), and the correlations between MST4 expression of the clinical HCC tissues, the clinicopathologic features, and survival were further evaluated. The effects of MST4 on HCC cell migratory and invasive properties in vitro were evaluated by Transwell and Boyden assays. The intrahepatic metastasis mouse model was established to evaluate the HCC metastasis in vivo. The PI3K inhibitor, LY294002, and a specific siRNA against Snail1 were used to investigate the roles of PI3K/AKT pathway and Snail1 in MST4-regulated EMT, migration, and invasion of HCC cells, respectively. Results: In this study, by comprehensively analyzing our clinical data, we discovered that low MST4 expression is highly associated with the advanced progression of HCC and serves as a prognostic biomarker for HCC patients of clinical-stage III-IV. Functional studies indicate that MST4 inactivation induces epithelial-to-mesenchymal transition (EMT) of HCC cells, promotes their migratory and invasive potential in vitro, and facilitates their intrahepatic metastasis in vivo, whereas MST4 overexpression exhibits the opposite phenotypes. Mechanistically, MST4 inactivation elevates the expression and nuclear translocation of Snail1, a key EMT transcription factor (EMT-TF), through the PI3K/AKT signaling pathway, thus inducing the EMT phenotype of HCC cells, and enhancing their invasive and metastatic potential. Moreover, a negative correlation between MST4 and p-AKT, Snail1, and Ki67 and a positive correlation between MST4 and E-cadherin were determined in clinical HCC samples. Conclusions: Our findings indicate that MST4 suppresses EMT, invasion, and metastasis of HCC cells by modulating the PI3K/AKT/Snail1 axis, suggesting that MST4 may be a potential prognostic biomarker for aggressive and metastatic HCC.
Collapse
Affiliation(s)
- Mei-Juan Dian
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.,Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
| | - Jing Li
- Radiotherapy Center, the First People's Hospital of Chenzhou, Xiangnan University, Chenzhou 423000, China
| | - Xiao-Ling Zhang
- Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China
| | - Zi-Jian Li
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Ying Zhou
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Wei Zhou
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Qiu-Ling Zhong
- State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Wen-Qian Pang
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xiao-Lin Lin
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Tao Liu
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yi-An Liu
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yong-Long Li
- Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
| | - Liu-Xin Han
- The third people's hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China
| | - Wen-Tao Zhao
- Department of Gastrointestinal Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming 650118, China
| | - Jun-Shuang Jia
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Sheng-Jun Xiao
- Department of Pathology, the Second Affiliated Hospital, Guilin Medical University, Guilin 541199, China
| | - Dong Xiao
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.,Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
| | - Jia-Wei Xia
- The third people's hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China
| | - Wei-Chao Hao
- Department of Oncology, The First Affiliation Hospital of Guangdong Pharmaceutical University, Guangzhou 510062, China
| |
Collapse
|
|
36
|
Morisue R, Kojima M, Suzuki T, Nakatsura T, Ojima H, Watanabe R, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Ishii G, Gotohda N, Fujiwara T, Ochiai A. Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses. Int J Cancer 2021; 149:546-560. [PMID: 33662146 DOI: 10.1002/ijc.33545] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 12/23/2020] [Accepted: 01/27/2021] [Indexed: 12/14/2022]
Abstract
Sarcomatoid hepatocellular carcinoma (SHCC), which was a rare histological subtype of hepatocellular carcinoma (HCC), is currently subclassified as poorly differentiated HCC because of insufficient evidence to define SHCC as a subtype of HCC. We aimed to assess the feasibility of classifying SHCC as a histological subtype of HCC by comprehensively identifying novel and distinct characteristics of SHCC compared to ordinary HCC (OHCC). Fifteen SHCCs (1.4%) defined as HCC with at least a 10% sarcomatous component, 15 randomly disease-stage-matched OHCCs and 163 consecutive OHCCs were extracted from 1106 HCCs in the Pathology Database (1997-2019) of our hospital. SHCC patients showed poor prognosis, and the tumors could be histologically subclassified into the pleomorphic, spindle and giant cell types according to the subtype of carcinomas with sarcomatoid or undifferentiated morphology in other organs. The transcriptomic analysis revealed distinct characteristics of SHCC featuring the upregulation of genes associated with epithelial-to-mesenchymal transition and inflammatory responses. The fluorescent multiplex immunohistochemistry results revealed prominent programmed death-ligand 1 (PD-L1) expression on sarcomatoid tumor cells and higher infiltration of CD4+ and CD8+ T cells in SHCCs compared to OHCCs. The density of CD8+ T cells in the nonsarcomatous component of SHCCs was also higher than that in OHCCs. In conclusion, the comprehensive analyses in our study demonstrated that SHCC is distinct from OHCC in terms of clinicopathologic, transcriptomic and immunologic characteristics. Therefore, it is reasonable to consider SHCC as a histological subtype of HCC.
Collapse
Affiliation(s)
- Ryo Morisue
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.,Department of Gastroenterological Surgery Transplant and Surgical Oncology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.,Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | - Motohiro Kojima
- Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | - Toshihiro Suzuki
- Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.,General Medical Education and Research Center, Teikyo University, Tokyo, Japan
| | - Tetsuya Nakatsura
- Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | - Hidenori Ojima
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Reiko Watanabe
- Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.,Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan
| | - Motokazu Sugimoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Shin Kobayashi
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Shinichiro Takahashi
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Masaru Konishi
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Genichiro Ishii
- Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.,Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan
| | - Naoto Gotohda
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery Transplant and Surgical Oncology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Atsushi Ochiai
- Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| |
Collapse
|
|
37
|
Huang SC, Liao SH, Su TH, Jeng YM, Kao JH. Clinical manifestations and outcomes of patients with scirrhous hepatocellular carcinoma. Hepatol Int 2021; 15:472-481. [PMID: 33544314 DOI: 10.1007/s12072-021-10146-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 01/17/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND The scirrhous hepatocellular carcinoma (HCC) is a rare subtype characterized by prominent fibrous stroma separating nests of tumor cells histologically. The clinical characteristics of scirrhous HCC have not been clearly elucidated due to limited literatures. We aimed to investigate the clinical manifestations and outcomes of patients with scirrhous HCC. METHODS A total of 4012 patients with histologically proven HCC from the Cancer Registry Database (2004-2016) of the National Taiwan University Hospital (NTUH) were enrolled; whereas, 30 patients with scirrhous HCC were identified from the pathology database of NTUH. We matched 120 patients with non-scirrhous HCC through propensity score according to sex, age, Barcelona Clinic Liver Cancer stage and initial treatment modality for comparison. RESULTS No significant difference in baseline characteristics and presentations was observed between the patients with scirrhous and non-scirrhous HCC except baseline alpha-fetoprotein level. The overall survival was comparable in these two groups. For the patients undergoing curative therapy, the risk of recurrence in the patients with scirrhous HCC was significantly higher within 24 months after curative therapy (hazard ratio [HR], 2.88, 95% confidence interval [CI], 1.43-5.80, p value, 0.003) as compared with those with non-scirrhous HCC. The overall recurrence rate was comparable in these two groups. CONCLUSIONS Using propensity score matching, the risk of recurrence in the patients with scirrhous HCC was significantly higher in the first 2 years after curative therapy as compared to those with non-scirrhous HCC. An individualized post-curative treatment monitoring strategy should be considered for the patients with scirrhous HCC.
Collapse
Affiliation(s)
- Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Yung-Ming Jeng
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St., Taipei, 10002, Taiwan.
| |
Collapse
|
|
38
|
Giannis D, Morsy S, Geropoulos G, Esagian SM, Sioutas GS, Moris D. The Epidemiology, Staging and Outcomes of Sarcomatoid Hepatocellular Carcinoma: A SEER Population Analysis. In Vivo 2021; 35:393-399. [PMID: 33402488 PMCID: PMC7880738 DOI: 10.21873/invivo.12270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/11/2020] [Accepted: 10/13/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) subtypes differ in terms of histopathology and prognosis. Sarcomatoid HCC is rare and literature concerning the survival of patients with sarcomatoid HCC is scarce. MATERIALS AND METHODS Data of patients with sarcomatoid HCC, diagnosed from 1989 to 2016, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We evaluated the baseline and tumor related data, overall survival (OS), disease-specific survival and the performance (Harrell's concordance index - OS c-index) of the eighth edition of the American Joint Committee on Cancer TNM staging system (AJCC8). In addition, univariate and multivariate forward stepwise cox regression analyses were performed to identify factors associated with increased risk of death. RESULTS The SEER cohort consisted of 71 patients, mostly males (n=49, 69.0%), of White race (n=51, 71.8%) and the most common stage at presentation was stage IVB (n=30, 42.3%). The overall predictive ability of AJCC8 was mediocre, with an OS c-index=0.577 (SE=0.048). Surgery (hazard ratio=0.25, p<0.001) was significantly associated with reduced risk of death. Advanced TNM stage was not associated with increased risk of death. CONCLUSION Sarcomatoid HCC, a rare subtype of HCC, is associated with poor outcomes in terms of overall and disease-specific survival across all disease stages. Surgery seems to be of utmost importance. The eighth edition of the AJCC8 for HCC underperforms in predicting the survival of patients with sarcomatoid subtype.
Collapse
Affiliation(s)
- Dimitrios Giannis
- Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Sara Morsy
- Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Georgios Geropoulos
- Thoracic Surgery Department, University College London Hospitals, NHS; Foundation Trust, London, U.K
| | - Stepan M Esagian
- Faculty of Medicine, Democritus University of Thrace, Dragana, Alexandroupolis, Greece
| | - Georgios S Sioutas
- Faculty of Medicine, Democritus University of Thrace, Dragana, Alexandroupolis, Greece
| | - Dimitrios Moris
- Duke Surgery, Duke University Medical Center, Durham, NC, U.S.A.
| |
Collapse
|
|
39
|
Vyas M, Jain D. An update on subtypes of hepatocellular carcinoma: From morphology to molecular. INDIAN J PATHOL MICR 2021; 64:S112-S120. [PMID: 34135152 DOI: 10.4103/ijpm.ijpm_751_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The morphologic spectrum of hepatocellular carcinoma (HCC) is quite broad. While in about one-third of cases, the neoplasms can be categorized into meaningful subtypes based on morphology, a vast majority of these neoplasms are morphologically heterogeneous. With extensive tumor profiling, data has begun to emerge which can correlate specific morphologic features with underlying molecular signatures. A true morphologic subtype not only has reproducible H & E features, further supported by specific immunohistochemical or molecular signatures, but also has specific clinical implications and prognostic associations. Eight such morphologic subtypes are recognized by the 2019 WHO classification of tumors with a few more additional subtypes described in the literature. The goal of this review is to familiarize the reader with the morphologic subtypes and elaborate on the clinical and molecular associations of these neoplasms.
Collapse
Affiliation(s)
- Monika Vyas
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Dhanpat Jain
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| |
Collapse
|
|
40
|
Tang Y, Zhang T, Zhao Y, Chen Z, Ma X. Development and validation of a comprehensive radiomics nomogram for prognostic prediction of primary hepatic sarcomatoid carcinoma after surgical resection. Int J Med Sci 2021; 18:1711-1720. [PMID: 33746587 PMCID: PMC7976557 DOI: 10.7150/ijms.53602] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 01/06/2021] [Indexed: 02/05/2023] Open
Abstract
Objective: This study aimed to establish and validate a radiomics nomogram comprised of clinical factors and radiomics signatures to predict prognosis of primary hepatic sarcomatoid carcinoma (PHSC) patients after surgical resection. Methods: In this retrospective study, 79 patients with pathological confirmation of PHSC and underwent surgical resection were recruited. A radiomics nomogram was developed by radiomics signatures and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by nomogram. Model performance and clinical usefulness were assessed by C-index, calibration curve, decision curve analysis (DCA) and survival curve. Results: A total of 79 PHSC were included with 1-year and 3-year overall survival rates of 63.3% and 35.4%, respectively. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found six independent prognostic factors. The radiomics nomogram showed a significant prediction value with overall survival (HR: 7.111, 95%CI: 3.933-12.858, P<0.001). C-index of nomogram was 0.855 and 0.829 in training and validation set, respectively. Decision curve analysis validated the clinical utility of this nomogram. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole cohort (30.6% vs. 90.1% and 5.6% vs. 62.4%, respectively, P < 0.001). Conclusion: This radiomics nomogram serve as a potential tool for predicting prognosis of PHSC after surgical resection, and help to identify high risk patients who may obtain feeble survival benefit from surgical resection.
Collapse
Affiliation(s)
- Youyin Tang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China
| | - Tao Zhang
- West China School of Medicine, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China
| | - Yunuo Zhao
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China
| | - Zheyu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China
| | - Xuelei Ma
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China
| |
Collapse
|
|
41
|
Numbere N, Zhang D, Agostini-Vulaj D. A rare histologic subtype of hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma: report of a case. Hepat Oncol 2020; 8:HEP33. [PMID: 34084452 PMCID: PMC8162176 DOI: 10.2217/hep-2020-0027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Worldwide, primary liver cancer is the fourth leading cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of HCC with conventional HCC admixed with areas with sarcomatoid morphology. SHC is an aggressive, rapidly growing tumor with unfavorable prognosis. Pedunculated SHC is an uncommon presentation of SHC. Due to its rarity, much remains unknown about the etiopathogenesis, molecular underpinnings, and treatment of SHC. We present a case of an exophytic SHC arising in a background of cirrhosis in an older adult. A resection was performed, but the patient subsequently developed multiple additional intrahepatic metastatic lesions necessitating further treatment with chemotherapy.
Collapse
Affiliation(s)
- Numbereye Numbere
- Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Dongwei Zhang
- Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Diana Agostini-Vulaj
- Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| |
Collapse
|
|
42
|
Abstract
A 51-year-old woman with a history of sarcomatoid hepatocellular carcinoma, status post resection, underwent FDG PET/CT. In addition to abnormal activity elsewhere, the images showed focal activity in the isthmus of the thyroid, suggestive of malignant involvement, and diffuse mild activity in the left lobe of the thyroid, suggestive of thyroiditis. After a 10-week anti-PD-1 pembrolizumab therapy, the follow-up FDG PET/CT scan demonstrated much more intense activity in both the isthmus and the left lobe of the thyroid. Pathological examination revealed papillary thyroid cancer in the isthmus and thyroiditis in the left lobe of the thyroid.
Collapse
|
|
43
|
Li J, Wei T, Zhang J, Wei S, Chen Q, Chen BW, Zhou Y, Wen L, Qin H, Bai X, Liang T. Carcinosarcoma of the pancreas: comprehensive clinicopathological and molecular characterization. HPB (Oxford) 2020; 22:1590-1595. [PMID: 32081541 DOI: 10.1016/j.hpb.2020.01.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/26/2020] [Accepted: 01/28/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Carcinosarcoma of pancreas is a rare subtype of pancreatic cancer. The aim of this study was to comprehensively elaborate the clinicopathological and molecular features of this rare malignancy. METHODS Patients who were diagnosed with carcinosarcoma of the pancreas were retrospectively identified from pathology database of a single institution between 2012 and 2018. RESULTS A total of nine patients were identified. Pathological examination of tumor tissues from included patients showed coexisting carcinomatous and sarcomatous components. These two components were distinguished by mutually exclusive expression of cytokeratin and vimentin. The sarcomatous tissue exhibited more extensive proliferation, as revealed by Ki67 staining, and necrosis compared with the carcinomatous counterpart. Genomic analysis of tumor tissues for two patients demonstrated hotspot mutation at KRAS and TP53. Carcinomatous and sarcomatous components were separately obtained via laser captured microdissection in one patient, and mutations of driving genes were highly concordant between them. Besides, immunostaining of frequently-altered tumor suppressor genes for these two components suggested consistent expression patterns. The median overall survival for six patients with adequate follow-up was 14 months. CONCLUSION Carcinosarcoma of the pancreas represent a rare malignancy with distinct histological characteristics. Genomic and molecular analysis suggested monoclonal origin of carcinomatous and sarcomatous components.
Collapse
Affiliation(s)
- Jin Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Tao Wei
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Jian Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Shumei Wei
- Department of Pathology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China
| | - Qi Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Bryan Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Yue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Liang Wen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Hao Qin
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang, China.
| |
Collapse
|
|
44
|
Matsui HM, Hazama S, Nakajima M, Xu M, Matsukuma S, Tokumitsu Y, Shindo Y, Tomochika S, Yoshida S, Iida M, Suzuki N, Takeda S, Yoshino S, Ueno T, Oka M, Nagano H. Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial. Cancer Immunol Immunother 2020; 70:945-957. [PMID: 33074442 DOI: 10.1007/s00262-020-02737-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 10/02/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION A proteomic analysis of hepatocellular carcinoma (HCC) has revealed that Heat Shock Protein 70 (HSP70) is among the cancer antigen proteins of HCC. Moreover, we confirmed that HSP70 was highly expressed in HCC by immunohistochemical staining. Based on these results, we developed an HSP70 mRNA-transfected dendritic cell (DC) therapy for treating unresectable or recurrent HCC, and the phase I trial was completed successfully. Thus, we aimed to investigate the safety and efficacy of this therapy as a postoperative adjuvant treatment after curative resection for HCC to prevent recurrence by conducting a phase I/II randomized controlled clinical trial. METHODS Patients (n = 45) with resectable HCC of stages II-IVa were registered and randomly assigned into two groups (DC group: 31 patients, control group: 14 patients) before surgery. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were safety and overall survival. The DC therapy was initially administered at approximately 1 week after surgery, and twice every 3-4 weeks thereafter. RESULTS No adverse events specific to the immunotherapy were observed in the DC group. There was no difference in DFS between the DC and control groups (p = 0.666). However, in the subgroup with HSP70-expressing HCC, DFS of the DC group tended to be better (p = 0.090) and OS of the DC group was significantly longer (p = 0.003) than those of the control group. CONCLUSION The HSP70 mRNA-transfected DC therapy was performed safely as an adjuvant therapy. The prognosis of HSP70-expressing HCC cases could be expected to improve with this therapy.
Collapse
Affiliation(s)
- Hiroto Matsui Matsui
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Shoichi Hazama
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.,Department of Translational Research and Developmental Therapeutics Against Cancer, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
| | - Masao Nakajima
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Ming Xu
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Satoshi Matsukuma
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Yukio Tokumitsu
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Yoshitaro Shindo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Shinobu Tomochika
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Shin Yoshida
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Michihisa Iida
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Nobuaki Suzuki
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Shigeru Takeda
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Shigefumi Yoshino
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.,Yamaguchi University Hospital Cancer Center, Ube, Yamaguchi, Japan
| | - Tomio Ueno
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Masaaki Oka
- Yamaguchi University, Yamaguchi, Yamaguchi, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
| |
Collapse
|
|
45
|
Zhu SG, Li HB, Yuan ZN, Liu W, Yang Q, Cheng Y, Wang WJ, Wang GY, Li H. Achievement of complete response to nivolumab in a patient with advanced sarcomatoid hepatocellular carcinoma: A case report. World J Gastrointest Oncol 2020; 12:1209-1215. [PMID: 33133387 PMCID: PMC7579730 DOI: 10.4251/wjgo.v12.i10.1209] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 07/06/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of hepatocellular carcinoma (HCC), with a high recurrence rate after surgery. In addition to limited effective treatment for the advanced stage of SHC, the prognosis of patients with this malignancy is worse than that of patients with conventional HCC. CASE SUMMARY We present the case of a 54-year-old man with SHC who underwent radical segmental hepatectomy, which relapsed 4 mo after surgery due to lymphatic metastasis in the porta hepatis. Although a second surgery was performed, new metastasis developed in the mediastinal lymph nodes. Therefore, sorafenib and lenvatinib were sequentially administered as first- and second-line systemic therapies, respectively. However, progressive disease was confirmed based on a recurrent hepatic lesion and new metastatic lesion in the abdominal cavity. Percutaneous transhepatic cholangial drainage was performed to alleviate the biliary obstruction. Because the tumor was strongly positive for programmed death-ligand 1, the patient was started on nivolumab. Imaging studies revealed that after two cycles of immunotherapy, the metastatic lesions decreased to undetectable levels. CONCLUSION The patient experienced continuous complete remission for 8 mo. Immune checkpoint inhibitors are useful for the treatment of advanced SHC.
Collapse
Affiliation(s)
- Shu-Guang Zhu
- Department of Hepatic Surgery and Liver Transplantation, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
| | - Hai-Bo Li
- Department of Hepatic Surgery and Liver Transplantation, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
- Liver Transplant Branch of Organ Transplant Center, Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
| | - Ze-Nan Yuan
- Department of Hepatic Surgery and Liver Transplantation, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
| | - Wei Liu
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
| | - Qing Yang
- Department of Hepatic Surgery and Liver Transplantation, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
| | - Ying Cheng
- Department of Medicine, OrigiMed Inc., Shanghai 201100, China
| | - Wen-Jing Wang
- Department of Medicine, OrigiMed Inc., Shanghai 201100, China
| | - Guo-Ying Wang
- Department of Hepatic Surgery and Liver Transplantation, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
| | - Hua Li
- Department of Hepatic Surgery and Liver Transplantation, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
- Liver Transplant Branch of Organ Transplant Center, Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
| |
Collapse
|
|
46
|
Wang JP, Yao ZG, Sun YW, Liu XH, Sun FK, Lin CH, Ren FX, Lv BB, Zhang SJ, Wang Y, Meng FY, Zheng SZ, Gong W, Liu J. Clinicopathological characteristics and surgical outcomes of sarcomatoid hepatocellular carcinoma. World J Gastroenterol 2020; 26:4327-4342. [PMID: 32848337 PMCID: PMC7422543 DOI: 10.3748/wjg.v26.i29.4327] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/24/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated.
AIM To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC.
METHODS In total, 196 patients [41 sarcomatoid HCC and 155 high-grade (Edmondson-Steiner grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated.
RESULTS Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components.
CONCLUSION Sarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.
Collapse
Affiliation(s)
- Jian-Ping Wang
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Zhi-Gang Yao
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Ya-Wen Sun
- Cancer Prevention and Control Research Office of Shandong Province, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
| | - Xi-Han Liu
- Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Feng-Kai Sun
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Cun-Hu Lin
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Fu-Xin Ren
- Shandong Medical Imaging Research Institute, Shandong University, Jinan 250021, Shandong Province, China
| | - Bei-Bei Lv
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Shuai-Jun Zhang
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Yang Wang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Fan-Ying Meng
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Shun-Zhen Zheng
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Wei Gong
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Jun Liu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| |
Collapse
|
|
47
|
Development and Validation of a Nomogram-Based Prognostic Evaluation Model for Sarcomatoid Hepatocellular Carcinoma. Adv Ther 2020; 37:3185-3205. [PMID: 32436026 DOI: 10.1007/s12325-020-01357-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of liver cancer with extremely poor prognosis. This study aimed to identify the prognostic factors and develop an exclusive and efficient nomogram to predict cancer-specific survival (CSS) for SHC. METHODS The data on patients diagnosed with SHC from January 1973 to December 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, and these patients were included as the training cohort. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression analyses were used to identify the prognostic risk factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to compare the clinical benefits of the prognostic evaluation model (PEM) with that of the American Joint Committee on Cancer (AJCC) staging system. The results were validated with an external validation cohort. RESULTS In total, 116 patients with SHC were included in the training cohort. Multivariate Cox analysis revealed M stage (distant metastasis), primary tumor surgery, and chemotherapy to be associated with CSS, and along with tumor size, an integrated PEM was constructed. A calibration curve for the probability of survival showed good agreement between the nomogram and actual observation. The C-index value of the nomogram for predicting CSS and AJCC was 0.853 and 0.649, respectively. In the validation cohort, the C-index value of the PEM discrimination was better than that of the Barcelona Clinic Liver Cancer (BCLC) staging system, CLIP score, and Okuda staging system, and no statistical difference was observed with eighth edition of the AJCC staging system and Izumi staging system. CONCLUSION The proposed four-factor nomogram of PEM could accurately predict the prognosis of SHC and could be used in clinical practice.
Collapse
|
|
48
|
Farooq A, Merath K, Paredes AZ, Wu L, Tsilimigras DI, Hyer JM, Sahara K, Mehta R, Beal EW, Pawlik TM. Outcomes of Patients with Scirrhous Hepatocellular Carcinoma: Insights from the National Cancer Database. J Gastrointest Surg 2020; 24:1049-1060. [PMID: 31243715 DOI: 10.1007/s11605-019-04282-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 05/20/2019] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Scirrhous hepatocellular carcinoma (HCC) is a rare primary liver tumor characterized by extensive fibrosis and production of parathyroid hormone-related peptide. There have been conflicting reports on patient survival in scirrhous versus non-scirrhous HCC. The objective of the present study was to define the clinical features, practice patterns, and long-term outcomes of patients with scirrhous HCC versus non-scirrhous HCC in a propensity score-matched cohort. METHODS A propensity score-matched cohort was created using data from the National Cancer Database for 2004 to 2015. A multivariable Cox proportional hazards regression analysis was performed to assess the effect of the scirrhous HCC variant on overall survival. RESULTS Among the 70,426 patients with a diagnosis of HCC who met the inclusion criteria, 99.8% had non-scirrhous HCC (n = 70,290) whereas a small subset had scirrhous HCC (n = 136, 0.19%). While 20,330 (28.9%) patients underwent liver-directed therapy (resection, ablation, and transplantation), the majority did not (n = 50,096, 71.1%). After propensity matching, there were no difference in 1-, 3-, or 5-year overall survival among patients with scirrhous versus non-scirrhous HCC (1-year overall survival (OS), 53.7% versus 51.0%; 3-year OS, 34.6% versus 28.7%; and 5-year OS, 18.0% versus 21.0%, respectively; p = 0.52). While the scirrhous HCC variant was not associated with survival (hazard ratio [HR] 0.93, 95% CI 0.74-1.16), non-receipt of liver-directed therapy (HR 0.24, 95% CI 0.18-0.32), advanced AJCC stage (III/IV) (HR 2.14, 95% CI 1.55-2.95), and non-academic facilities (HR 0.60, 95% CI 0.49-0.73) remained associated with worse survival. CONCLUSION Patients with the scirrhous variant had a comparable overall survival compared with individuals who had non-scirrhous HCC. Failure to receive liver-directed therapy, advanced AJCC stage (III/IV), and treatment at a non-academic facility was strongly associated with a worse long-term prognosis.
Collapse
Affiliation(s)
- Ayesha Farooq
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Katiuscha Merath
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Anghela Z Paredes
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Lu Wu
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - J Madison Hyer
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Kota Sahara
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Rittal Mehta
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Eliza W Beal
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
| |
Collapse
|
|
49
|
Martins-Filho SN, Putra J. Hepatic mesenchymal hamartoma and undifferentiated embryonal sarcoma of the liver: a pathologic review. Hepat Oncol 2020; 7:HEP19. [PMID: 32647564 PMCID: PMC7338921 DOI: 10.2217/hep-2020-0002] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
This review highlights two rare entities that are predominantly seen in children: hepatic mesenchymal hamartoma (HMH) and undifferentiated embryonal sarcoma of the liver (UESL). HMH is a benign lesion predominantly seen in the first 2 years of life, while UESL is malignant and usually identified in patients between 6 and 10 years of age. UESL may arise in the background of HMH, and the association has been supported by similar chromosomal aberrations (19q13.4). The diagnosis of both lesions is primarily based on histologic evaluation, as the clinical and radiological features are not always typical. The clinicopathologic characteristics, pathogenesis, differential diagnoses and treatment for both lesions are discussed.
Collapse
Affiliation(s)
- Sebastiao N Martins-Filho
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.,Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Juan Putra
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.,Division of Pathology, Department of Paediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Ontario, Canada
| |
Collapse
|
|
50
|
Chen CY, Chen CC, Chuang WY, Leu YL, Ueng SH, Hsueh C, Yeh CT, Wang TH. Hydroxygenkwanin Inhibits Class I HDAC Expression and Synergistically Enhances the Antitumor Activity of Sorafenib in Liver Cancer Cells. Front Oncol 2020; 10:216. [PMID: 32158695 PMCID: PMC7052045 DOI: 10.3389/fonc.2020.00216] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 02/07/2020] [Indexed: 12/13/2022] Open
Abstract
Abnormal histone deacetylase (HDAC) expression is closely related to cancer development and progression. Many HDAC inhibitors have been widely used in cancer treatment; however, severe side effects often limit their clinical application. In this study, we attempted to identify natural compounds with HDAC inhibitory activity and low physiological toxicity and explored their feasibility and mechanisms of action in liver cancer treatment. A yeast screening system was used to identify natural compounds with HDAC inhibitory activity. Further, western blotting was used to verify inhibitory effects on HDAC in human liver cancer cell lines. Cell functional analysis was used to explore the effects and mechanisms and the in vitro results were verified in BALB/c nude mice. We found that hydroxygenkwanin (HGK), an extract from Daphne genkwa, inhibited class I HDAC expression, and thereby induced expression of tumor suppressor p21 and promoted acetylation and activation of p53 and p65. This resulted in the inhibition of growth, migration, and invasion of liver cancer cells and promoted cell apoptosis. Animal models revealed that HGK inhibited tumor growth in a synergistic manner with sorafenib. HGK inhibited class I HDAC expression and had low physiological toxicity. It has great potential as an adjuvant for liver cancer treatment and may be used in combination with anticancer drugs like sorafenib to improve therapeutic efficacy.
Collapse
Affiliation(s)
- Chi-Yuan Chen
- Tissue Bank, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Chin-Chuan Chen
- Tissue Bank, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan
| | - Wen-Yu Chuang
- Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taoyuan, Taiwan
| | - Yann-Lii Leu
- Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan.,Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.,Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Shir-Hwa Ueng
- Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taoyuan, Taiwan
| | - Chuen Hsueh
- Tissue Bank, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taoyuan, Taiwan
| | - Chau-Ting Yeh
- Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tong-Hong Wang
- Tissue Bank, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| |
Collapse
|