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Li X, Ma K, Ma X, Zhao X, Fan M, Xu Y. Lung enteric-type adenocarcinoma with gastric metastasis: a rare case report and literature review. Front Immunol 2024; 15:1486214. [PMID: 39507527 PMCID: PMC11537902 DOI: 10.3389/fimmu.2024.1486214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
Lung enteric-type adenocarcinoma (ETAC) is a rare subtype of non-small cell lung cancer (NSCLC), comprising approximately 0.6% of all primary lung adenocarcinomas. It is characterized by a tendency for early metastasis and a prognosis comparable to that of common lung adenocarcinoma. This case report described a patient with lung-ETAC who developed gastric metastasis. The patient underwent treatment with chemotherapy and a PD-1 inhibitor, resulting in disease remission with a progression-free survival (PFS) of 8 months. The follow-up time was 13 months. This case report was aimed to enhance understanding of the biological behavior of this rare tumor and provide insights into potential future treatment strategies.
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Affiliation(s)
- Xiaoning Li
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Kewei Ma
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xiaobo Ma
- Department of Pathology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xiangye Zhao
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Mengge Fan
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yinghui Xu
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China
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Luo ZH, Luo XY, Luo XQ, Jin AF, Zeng QY. Case report: 18F-FDG PET/CT in pulmonary enteric adenocarcinoma. Front Oncol 2024; 14:1447453. [PMID: 39469650 PMCID: PMC11513299 DOI: 10.3389/fonc.2024.1447453] [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: 06/11/2024] [Accepted: 09/23/2024] [Indexed: 10/30/2024] Open
Abstract
Pulmonary enteric adenocarcinoma (PEAC), an uncommon variant of lung cancer, presents significant diagnostic challenges due to its overlapping characteristics with colorectal adenocarcinomas. We present a case of a 55-year-old non-smoking female patient diagnosed with PEAC. The patient's initial symptoms included fever, cough, and sputum production, with air space consolidation on CT, leading to an initial diagnosis of pneumonia. Sputum culture after admission showed no growth of bacteria and fungi. Anti-inflammatory therapy was not ideal. Subsequent bronchoscopy with endobronchial ultrasound and biopsy confirmed the diagnosis of PEAC. Gastroscopy and colonoscopy yielded negative results, and a PET/CT scan revealed an FDG-avid lesion in the right middle lobe, with no other significant hypermetabolic gastrointestinal lesions, thereby excluding an extrapulmonary primary gastrointestinal malignancy. The patient was ultimately staged as PEAC (T4N1M0, stage IIIb). She declined anti-tumor therapy and experienced clinical deterioration during follow-up. This case report expands the radiological spectrum of PEAC, adds to the limited literature, and emphasizes the role of 18F-FDG PET/CT in diagnosing such diseases. It also underscores the importance of a multidisciplinary approach in the management of PEAC.
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Affiliation(s)
- Zhe-Huang Luo
- Department of Nuclear Medicine, Jiangxi Provincial People’s Hospital, the First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Xiao-Yan Luo
- Clinical Laboratory, Jiangxi Provincial Children’s Hospital, Children's Hospital Affiliated to Nanchang Medical College, Nanchang, China
| | - Xiu-Qin Luo
- Cardio-Thoracic Surgery, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Ai-Fang Jin
- Department of Nuclear Medicine, Jiangxi Provincial People’s Hospital, the First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Qing-Yun Zeng
- Department of Nuclear Medicine, Jiangxi Provincial People’s Hospital, the First Affiliated Hospital of Nanchang Medical College, Nanchang, China
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Kraus FM, Traut A, Nilius G, Volmerig J, Koziorowski A, Stöver I, Grabellus F, Stahl M, Christoph DC. Pulmonary Adenocarcinoma with Enteric Differentiation without TTF-1 Expression Is a Very Rare Subtype with Limited Treatment Options and Poor Prognosis. Oncology 2024:1-13. [PMID: 39159621 DOI: 10.1159/000540515] [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: 02/04/2024] [Accepted: 07/04/2024] [Indexed: 08/21/2024]
Abstract
INTRODUCTION Pulmonary adenocarcinoma with enteric differentiation (PAED) without thyroid transcription factor-1 (TTF-1) expression is an extremely rare variant of lung cancer. Due to its rarity, few clinicopathological and molecular studies have been performed on PAED, particularly in Caucasian patients. Therefore, it is necessary to obtain clinicopathological data of Caucasian PAED patients without TTF-1 expression, their systemic therapy options, and the efficacy of their systemic treatment. METHODS We examined the clinicopathological features of 121 cases of TTF-1-negative pulmonary adenocarcinoma at a certified German lung cancer center including 79 cases without a PAED and 42 cases with a PAED, compared these subgroups, and investigated patients' response to chemotherapy and immunotherapy as first-line treatment. By using endoscopy and/or a PET-CT, a primary adenocarcinoma of the digestive tract was excluded in all PAED patients. RESULTS A comparison of clinicopathological data of TTF-1-negative PAED and non-PAED patients revealed a significantly lower frequency of high programmed death receptor ligand 1 (PD-L1) expression in PAED resulting in the lack of single-agent immunotherapy (p = 0.032) in this subgroup. Frequencies of an activating Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation were high in both groups (46.7% and 50.0%), but G12C gene mutations were seldomly noted (in 6.7% and 18.5% of patients with evaluable data). Median overall survival (OS) was poor in both groups (10 and 12 months). The majority of PAED patients received platinum-based and taxane-containing chemotherapy or chemo-/immunotherapy with an objective response rate (ORR) of 31.6% and a disease control rate of 57.9%. Median progression-free survival (PFS) and OS of PAED patients with systemic therapy were very poor (3.9 months and 5.9 months). CONCLUSIONS Caucasian patients with TTF-1 negative PAED have a poor prognosis with a reduced ORR to standard first-line systemic therapy and short survival times (PFS and OS).
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Affiliation(s)
- Franziska Maria Kraus
- Department of Medical Oncology, Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany,
| | - Alexander Traut
- Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany
| | - Georg Nilius
- Department of Pneumology, Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany
- Germany and University Hospital Witten-Herdecke, Witten, Germany
| | - Jan Volmerig
- Department of Thoracic Surgery, Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany
| | | | - Imke Stöver
- Practice for Radio-Oncology Essen, Essen, Germany
| | | | - Michael Stahl
- Department of Medical Oncology, Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany
| | - Daniel C Christoph
- Department of Medical Oncology, Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany
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Liu J, Chang X, Qian L, Chen S, Xue Z, Wu J, Luo D, Huang B, Fan J, Guo T, Nie X. Proteomics-Derived Biomarker Panel Facilitates Distinguishing Primary Lung Adenocarcinomas With Intestinal or Mucinous Differentiation From Lung Metastatic Colorectal Cancer. Mol Cell Proteomics 2024; 23:100766. [PMID: 38608841 PMCID: PMC11092395 DOI: 10.1016/j.mcpro.2024.100766] [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: 09/12/2023] [Revised: 03/07/2024] [Accepted: 04/09/2024] [Indexed: 04/14/2024] Open
Abstract
The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical (IHC), and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging-based shotgun proteomics to characterize proteomes of formalin-fixed, paraffin-embedded tumor samples of PAIM (n = 22) and lmCRC (n = 17).Then three machine learning algorithms, namely support vector machine (SVM), random forest, and the Least Absolute Shrinkage and Selection Operator, were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by IHC to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection. The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of ten candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: CK7 (an established marker), NARR, MLPH, S100A14) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.
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Affiliation(s)
- Jiaying Liu
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaona Chang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liujia Qian
- Center for ProtTalks, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China
| | - Shuo Chen
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhangzhi Xue
- Center for ProtTalks, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China
| | - Junhua Wu
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Danju Luo
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Huang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Fan
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tiannan Guo
- Center for ProtTalks, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China.
| | - Xiu Nie
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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5
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Deng H. Utility of Immunohistochemistry in the Diagnosis of Pleuropulmonary and Mediastinal Cancers: A Review and Update. Arch Pathol Lab Med 2024; 148:267-283. [PMID: 37406295 DOI: 10.5858/arpa.2022-0483-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2023] [Indexed: 07/07/2023]
Abstract
CONTEXT.— Immunohistochemistry has become a valuable ancillary tool for the accurate classification of pleuropulmonary and mediastinal neoplasms necessary for therapeutic decisions and predicting prognostic outcome. Diagnostic accuracy has significantly improved because of the continuous discoveries of tumor-associated biomarkers and the development of effective immunohistochemical panels. OBJECTIVE.— To increase the accuracy of diagnosis and classify pleuropulmonary neoplasms through immunohistochemistry. DATA SOURCES.— Literature review and the author's research data and personal practice experience. CONCLUSIONS.— This review article highlights that appropriately selecting immunohistochemical panels enables pathologists to effectively diagnose most primary pleuropulmonary neoplasms and differentiate primary lung tumors from a variety of metastatic tumors to the lung. Knowing the utilities and pitfalls of each tumor-associated biomarker is essential to avoid potential diagnostic errors.
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Affiliation(s)
- Hongbing Deng
- From the Department of Pathology, Geisinger Commonwealth Medical School and Pathology, Geisinger Wyoming Valley Medical Center, Geisinger Health System, Wilkes-Barre, Pennsylvania
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Okada F, Takeda M, Fujii T, Uchiyama T, Sasaki S, Matsuoka M, Nitta Y, Terada C, Maebo K, Morita K, Ishida E, Sawabata N, Ohbayashi C. Clinicopathological and genetic analyses of pulmonary enteric adenocarcinoma. J Clin Pathol 2024; 77:111-115. [PMID: 36456172 DOI: 10.1136/jcp-2022-208583] [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: 09/07/2022] [Accepted: 11/21/2022] [Indexed: 12/03/2022]
Abstract
AIMS Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of pulmonary adenocarcinoma. Due to its rarity, few pathological and molecular studies have been performed on PEAC. We herein conducted clinicopathological, immunohistochemical and molecular analyses of PEAC with a focus on its differentiation from invasive mucinous adenocarcinoma (IMA). METHODS We examined the clinicopathological features of 16 cases of PEAC and performed a genetic analysis using next-generation sequencing (NGS). The results obtained were compared with those for IMA. RESULTS The average age of patients with PEAC (seven men and nine women) was 72.9 years. A comparison of clinical data on PEAC and IMA revealed no significant differences in age, sex or smoking history. Fifteen PEAC cases had dirty necrosis. Immunohistochemically, the positive rates for each antibody in PEAC were as follows: CK7, 88% (14/16); CK20, 81% (13/16); CDX2, 88% (14/16); p53, 69% (11/16); MUC1, 100% (16/16); MUC2, 19% (3/16); MUC5AC, 69% (11/16); MUC6, 19% (3/16). The positive rates for these antibodies in IMA were 100%, 87%, 0%, 7%, 93%, 0%, 100% and 80%, respectively. EGFR mutations, the MET exon 14 skipping mutation, BRAF mutations, the ALK fusion gene and ROS-1 fusion gene were not detected in any cases of PEAC or IMA. Among PEAC cases, NGS identified KRAS mutations in seven (44%, 7/16) and TP53 mutations in nine (56%, 9/16). Among IMA cases, the most commonly mutated gene was KRAS (90%). CONCLUSIONS The rates of dirty necrosis, immunopositivity for CDX2 and TP53 mutations were significantly higher, while that of KRAS mutations was significantly lower in PEAC cases than in IMA cases.
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Affiliation(s)
- Fumi Okada
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Maiko Takeda
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Tomomi Fujii
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Tomoko Uchiyama
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Shoh Sasaki
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Minami Matsuoka
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Yuji Nitta
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Chiyoko Terada
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Katsuya Maebo
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
| | - Kohei Morita
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
- Department of Diagnostic Pathology, Nara Prefecture General Medical Center, Nara, Japan
| | - Eiwa Ishida
- Department of Diagnostic Pathology, Nara Prefecture General Medical Center, Nara, Japan
| | - Noriyoshi Sawabata
- Department of Thoracic and Cardio-Vascular Surgery, Nara Medical University, Kashihara, Japan
| | - Chiho Ohbayashi
- Department of Diagnostic Pathology, Nara Medical University, Kashihara, Japan
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7
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Liu Y, Feng Z, Wei X, Yao P, Liu X, Jia Y, Zhang S, Yan W. Lymph node and bone metastasis of pulmonary intestinal adenocarcinoma: A case report. Oncol Lett 2023; 26:488. [PMID: 37818133 PMCID: PMC10561161 DOI: 10.3892/ol.2023.14075] [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: 06/21/2023] [Accepted: 09/13/2023] [Indexed: 10/12/2023] Open
Abstract
Pulmonary enteric adenocarcinoma (PEAC) is a rare pathological type of lung adenocarcinoma, accounting for ~0.6% of primary lung adenocarcinoma, which has similar morphological and immunohistochemical characteristics to colorectal adenocarcinoma. Making a certain differential diagnosis of PEAC based on morphological and immunohistochemical results is difficult. It is known that PEAC may metastasize to the pancreas, skin, soleus muscle and intestine, but no bone metastasis has been reported. At our department, a rare case of PEAC with bone and lymph node metastasis was previously diagnosed. The present case study reports on a 58-year-old male patient encountered at our hospital with pain in the lumbar, back and right iliac with no obvious cause. Chest CT indicated a space-occupying lesion in the left upper lung lobe, enlarged lymph nodes in the mediastinum and left lung, and partial vertebral bone destruction. Enhanced CT results indicated multiple foci of active bone metabolism in the body, while rectal colonoscopy showed no obvious abnormalities. Histopathological and immunohistochemical results after right iliac bone puncture suggested stage IV PEAC with secondary malignancies in bones, mediastinal lymph node, hilar lymph node and left supraclavicular lymph node.
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Affiliation(s)
- Yanbin Liu
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Zeyao Feng
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Xinyu Wei
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Peizhuo Yao
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Xuanyu Liu
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Yiwei Jia
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Shuqun Zhang
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Wanjun Yan
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
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Sugawara E, Shigematsu Y, Amori G, Sugita K, Yonese J, Takeuchi K, Inamura K. CDX2- and PAX8-Expressing Subtypes in Female Urethral Adenocarcinoma: Pathogenesis Insights through Immunohistochemical and Morphological Analyses. Diagnostics (Basel) 2023; 13:2408. [PMID: 37510152 PMCID: PMC10377779 DOI: 10.3390/diagnostics13142408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/13/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
Female urethral adenocarcinoma has attracted attention as a rare tumor type based on its differential pathogenesis from its male counterpart. However, to date, our knowledge concerning its immunohistochemical and morphological characteristics remains limited due to the small number of cases studied. In this study, nine consecutive cases of female urethral adenocarcinoma were used for immunohistochemical and morphological characterization of the tumor based on semi-comprehensive immunohistochemical analysis and detailed morphological evaluations. Our immunohistochemical assay revealed two subtypes of female urethral adenocarcinoma with distinctive staining patterns: the CDX2- and PAX8-expressing subtypes. The former stained positive for other intestinal markers (e.g., HNF4α and TFF1) as well (7 of 7 cases); the latter stained negative for these intestinal markers (0 of 2 cases) but stained positive for clear cell carcinoma markers (e.g., Napsin A and HNF1β) (2 of 2 cases). Regarding cytokeratins, the former displayed a CK7- and CK20-positive immunoprofile (7 of 7 cases); the latter exhibited a CK7-positive and CK20-negative immunoprofile (2 of 2 cases). Morphologically, CDX2- and PAX8-expressing subtypes resembled intestinal-type adenocarcinoma and clear cell carcinoma (occurring in gynecological organs), respectively. The semi-comprehensive immunoprofiling data presented in this study can potentially contribute to the correct diagnosis of this rare tumor type. Finally, our study represents an important basis for future investigations aiming to further elucidate the details and origin of female urethral adenocarcinoma, and it can potentially contribute to developing diagnostic and therapeutic strategies for treating this malignancy.
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Affiliation(s)
- Emiko Sugawara
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Yasuyuki Shigematsu
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Gulanbar Amori
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Keisuke Sugita
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Junji Yonese
- Department of Genitourinary Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Kengo Takeuchi
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Kentaro Inamura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
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Tchienga D, Ascio NM, Qureshi A, Razia S, Romulo G, Asarian A, Xiao P, Nouthe B, Belinga D. CK-7 negative primary lung adenocarcinoma. J Surg Case Rep 2023; 2023:rjad316. [PMID: 37332662 PMCID: PMC10271213 DOI: 10.1093/jscr/rjad316] [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: 04/28/2023] [Accepted: 05/11/2023] [Indexed: 06/20/2023] Open
Abstract
Cytokeratin (CK) 7 is normally expressed in the vast majority of lung adenocarcinoma (ADC). However, on rare occasions, as reported in this paper, CK7 negativity can challenge the diagnosis of pulmonary ADC. Hence, the need to use a combination of 'immunomarkers' such as thyroid transcription factor 1, Napsin A, p40, p63 and CK20.
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Affiliation(s)
- Dimitri Tchienga
- Correspondence address. St George’s University School of Medicine, True Blue, Grenada, WI, USA. Tel: 240-491-7864; E-mail:
| | - Noelani-Mei Ascio
- Department of Surgery, St George’s University School of Medicine, True Blue, Grenada, WI, USA
| | - Abid Qureshi
- Department of Surgery, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
| | - Sultana Razia
- Department of Surgery, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
| | - Genato Romulo
- Department of Surgery, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
| | - Armand Asarian
- Department of Surgery, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
| | - Philip Xiao
- Department of Pathology, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
| | - Brice Nouthe
- Fraser Health Authority/Department of Medicine, University of British Columbia, Vancouver, Canada
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10
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Fassi E, Mandruzzato M, Zamparini M, Bianchi S, Petrelli F, Baggi A, Alberti A, Grisanti S, Berruti A. Clinical presentation and outcome of patients with enteric-type adenocarcinoma of the lung: A pooled analysis of published cases. Lung Cancer 2023; 179:107176. [PMID: 37015149 DOI: 10.1016/j.lungcan.2023.107176] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 03/14/2023] [Accepted: 03/17/2023] [Indexed: 04/03/2023]
Abstract
Enteric-type adenocarcinoma of the lung (lung-ETAC, former pulmonary enteric adenocarcinoma, PEAC) is a rare subtype of non-small cell lung cancer (NSCLC), which shares morphological and immunohistochemical features with lung and colorectal adenocarcinoma. Few data are available on patient prognosis, possible prognostic factors and systemic approach to metastatic disease. We performed a pooled analysis and a systematic review of published lung-ETAC, along with an additional case description. Thirty-one eligible publications were identified, providing data from 126 patients. In the 127 patients overall analyzed, median overall survival (OS) was 56.0 (range 36.7-75.3) months in early-stage patients and 14.0 (range 4.5-23.5) months in those with advanced/metastatic disease. Median disease-free survival (DFS) after radical surgery was 24 (range 22.6-35.1) months. Smoking status (HR 4.304, 95% CI: 1.261-14.693, p = 0.020) and node involvement (HR 1.853, 95% CI: 1.179-2.911, p = 0.007) were the negative independent prognostic factors at multivariate analysis. As regards systemic therapies for advanced cases, no firm conclusions were drawn about the efficacy of lung cancer-oriented chemotherapy regimens as opposed to colon cancer-oriented ones. Molecular analysis of lung-ETAC revealed a relatively high mutational rate, with alterations in several druggable molecular pathways, KRAS and NRAS (31%) were the most frequently mutated oncogenes, followed by ROS1 (15%), RET (13%), BRAF (11%), EGFR (8%) and ALK (6%). Moreover, 3 (15%) out of 20 cases showed DNA mismatch repair deficiency (dMMR). In conclusion, advanced lung-ETAC patients appeared to have a better prognosis compared to other subtypes of NSCLC. Moreover, the mutational rate and microsatellite instability found in lung-ETACs suggest that a significant proportion of these patients could benefit from target therapies and immunotherapy.
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Affiliation(s)
- Elena Fassi
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy
| | - Marcella Mandruzzato
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy
| | - Manuel Zamparini
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy
| | - Susanna Bianchi
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy
| | | | - Alice Baggi
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy
| | - Andrea Alberti
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy
| | - Salvatore Grisanti
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy.
| | - Alfredo Berruti
- Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy
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11
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Liu Y, Lu T, Yuan M, Chen R, Lu J, Wang H, Wu Z, Wang Y. Genomic and transcriptomic insights into the precision treatment of pulmonary enteric adenocarcinoma. Lung Cancer 2023; 179:107169. [PMID: 37003209 DOI: 10.1016/j.lungcan.2023.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 02/18/2023] [Accepted: 03/09/2023] [Indexed: 03/13/2023]
Abstract
BACKGROUND Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung adenocarcinoma. More investigations about precision therapy in PEAC were required to improve the prognosis. METHODS Twenty-four patients with PEAC were enrolled in this study. Tumor tissue samples were available from 17 patients for both DNA and RNA based next-generation sequencing, PD-L1 IHC staining and PCR-based microsatellite instability (MSI) analysis. RESULTS TP53 (70.6%) and KRAS (47.1%) were the most frequently mutated genes in PEAC. For KRAS mutations, the prevalence of G12D (37.5%) and G12V (37.5%) was higher than G12A (12.5%) and G12C (12.5%). Actionable mutations in receptor tyrosine kinase (including one EGFR and two ALK mutations), PI3K/mTOR, RAS/RAF/MEK, homologous recombination repair (HRR) and cell cycle signaling pathways were identified in 94.1% of patients with PEAC. While PD-L1 expression was observed in 17.6% (3/17) patients, no MSI-H patients were identified. Transcriptomic data showed that two patients with positive PD-L1 expression had relatively high immune infiltration. In addition, prolonged survival was obtained with the treatment of osimertinib, ensartinib, and immunotherapy combined with chemotherapy in two EGFR-mutated, one ALK-rearranged, and one PD-L1 expressed patients, respectively. CONCLUSION PEAC is a disease of genetic heterogeneity. The administration of EGFR and ALK inhibitors was effective in patients with PEAC. PD-L1 expression and KRAS mutation type may be used as predictive biomarkers for immunotherapy in PEAC. This study provided both theoretical basis and clinical evidence for PEAC.
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12
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Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature. J Clin Med 2023; 12:jcm12041429. [PMID: 36835963 PMCID: PMC9965358 DOI: 10.3390/jcm12041429] [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: 12/30/2022] [Revised: 02/06/2023] [Accepted: 02/09/2023] [Indexed: 02/15/2023] Open
Abstract
Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.
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13
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Tang S, Li C, Wang Y, He Y. 68Ga-FAPI is superior to 18F-FDG in detection of micro-sized lung adenocarcinoma. Jpn J Clin Oncol 2023; 53:91-92. [PMID: 36156141 DOI: 10.1093/jjco/hyac153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/06/2022] [Indexed: 01/12/2023] Open
Affiliation(s)
- Shuaihu Tang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Chongjiao Li
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Yichun Wang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Yong He
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
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14
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Takanashi Y, Kurachi K, Fujihiro M, Sekihara K, Torii K, Kawase A, Matsubayashi Y, Hayakawa T, Baba S, Sugimura H, Iwashita T, Funai K. Thyroid transcription factor-1 expression in rectal adenocarcinoma metastatic to the lung. Respir Med Case Rep 2023; 42:101812. [PMID: 36660070 PMCID: PMC9842888 DOI: 10.1016/j.rmcr.2023.101812] [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: 11/13/2022] [Revised: 12/16/2022] [Accepted: 01/05/2023] [Indexed: 01/07/2023] Open
Abstract
Distinguishing metastatic lung tumors from primary lung cancer is essential for planning the appropriate treatment strategy. Thyroid transcription factor-1 (TTF-1) is a reliable immunohistochemistry (IHC) marker for differentiating between primary lung adenocarcinomas and metastatic lung tumors originating from colorectal adenocarcinomas. Herein, we report a rare case of TTF-1 expression in both the metastatic lung tumor and primary rectal adenocarcinoma. Aside from the similar histological characteristics of both tumors when stained with hematoxylin-eosin, the IHC patterns, including negative results for alveolar epithelium markers (napsin A and CK7) and positive results for intestinal markers (CK20, CDX2, SATB2, and β-catenin), of the lung tumor and the primary rectal adenocarcinoma strongly supported the final diagnosis. Considering the non-negligible frequency of TTF-1 positivity in colorectal adenocarcinomas, applying the IHC panel including multiple markers for alveolar epithelium and intestinal differentiation, would be helpful to support the diagnosis of metastatic lung tumor from a rectal adenocarcinoma.
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Affiliation(s)
- Yusuke Takanashi
- First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Kiyotaka Kurachi
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Mayu Fujihiro
- Department of Diagnostic Pathology, Hamamatsu University School of Medicine Hospital, Hamamatsu city, Shizuoka prefecture, Japan
| | - Keigo Sekihara
- First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Kakeru Torii
- First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Akikazu Kawase
- First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Yuta Matsubayashi
- First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Takamitsu Hayakawa
- First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Satoshi Baba
- Department of Diagnostic Pathology, Hamamatsu University School of Medicine Hospital, Hamamatsu city, Shizuoka prefecture, Japan
| | - Haruhiko Sugimura
- Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Toshihide Iwashita
- Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
| | - Kazuhito Funai
- First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu city, Shizuoka prefecture, Japan
- Corresponding author. First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
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15
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Lee JE, Do LN, Jeong WG, Lee HJ, Chae KJ, Kim YH, Park I. A Radiomics Approach on Chest CT Distinguishes Primary Lung Cancer from Solitary Lung Metastasis in Colorectal Cancer Patients. J Pers Med 2022; 12:jpm12111859. [PMID: 36579596 PMCID: PMC9695650 DOI: 10.3390/jpm12111859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 10/31/2022] [Accepted: 11/01/2022] [Indexed: 11/09/2022] Open
Abstract
PURPOSE This study utilized a radiomics approach combined with a machine learning algorithm to distinguish primary lung cancer (LC) from solitary lung metastasis (LM) in colorectal cancer (CRC) patients with a solitary pulmonary nodule (SPN). MATERIALS AND METHODS In a retrospective study, 239 patients who underwent chest computerized tomography (CT) at three different institutions between 2011 and 2019 and were diagnosed as primary LC or solitary LM were included. The data from the first institution were divided into training and internal testing datasets. The data from the second and third institutions were used as an external testing dataset. Radiomic features were extracted from the intra and perinodular regions of interest (ROI). After a feature selection process, Support vector machine (SVM) was used to train models for classifying between LC and LM. The performances of the SVM classifiers were evaluated with both the internal and external testing datasets. The performances of the model were compared to those of two radiologists who reviewed the CT images of the testing datasets for the binary prediction of LC versus LM. RESULTS The SVM classifier trained with the radiomic features from the intranodular ROI and achieved the sensitivity/specificity of 0.545/0.828 in the internal test dataset, and 0.833/0.964 in the external test dataset, respectively. The SVM classifier trained with the combined radiomic features from the intra- and perinodular ROIs achieved the sensitivity/specificity of 0.545/0.966 in the internal test dataset, and 0.833/1.000 in the external test data set, respectively. Two radiologists demonstrated the sensitivity/specificity of 0.545/0.966 and 0.636/0.828 in the internal test dataset, and 0.917/0.929 and 0.833/0.929 in the external test dataset, which were comparable to the performance of the model trained with the combined radiomics features. CONCLUSION Our results suggested that the machine learning classifiers trained using radiomics features of SPN in CRC patients can be used to distinguish the primary LC and the solitary LM with a similar level of performance to radiologists.
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Affiliation(s)
- Jong Eun Lee
- Department of Radiology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Luu Ngoc Do
- Department of Radiology, Chonnam National University, Gwangju, Korea
| | - Won Gi Jeong
- Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Hyo Jae Lee
- Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Kum Ju Chae
- Department of Radiology, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Yun Hyeon Kim
- Department of Radiology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Ilwoo Park
- Department of Radiology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
- Department of Radiology, Chonnam National University, Gwangju, Korea
- Department of Artificial Intelligence Convergence, Chonnam National University, Gwangju, Korea
- Department of Data Science, Chonnam National University, Gwangju, Korea
- Correspondence: ; Tel.: +82-62-220-5744; Fax: +82-62-226-4380
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16
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Gao J, Lu F, Yan J, Wang R, Xia Y, Wang L, Li L, Chang L, Li W. The role of radiotherapy-related autophagy genes in the prognosis and immune infiltration in lung adenocarcinoma. Front Immunol 2022; 13:992626. [PMID: 36311724 PMCID: PMC9606704 DOI: 10.3389/fimmu.2022.992626] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 09/27/2022] [Indexed: 11/17/2022] Open
Abstract
Background There is a close relationship between radiotherapy and autophagy in tumors, but the prognostic role of radiotherapy-related autophagy genes (RRAGs) in lung adenocarcinoma (LUAD) remains unclear. Methods Data used in the current study were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted gene co-expression network analysis (WGCNA) was executed to recognize module genes associated with radiotherapy. The differentially expressed genes (DEGs) between different radiotherapy response groups were filtered via edgeR package. The differentially expressed radiotherapy-related autophagy genes (DERRAGs) were obtained by overlapping the module genes, DEGs, and autophagy genes (ATGs). Then, prognostic autophagy genes were selected by Cox analyses, and a risk model and nomogram were subsequently built. Gene Set Enrichment Analysis (GSEA) and single-sample Gene Set Enrichment Analysis (ssGSEA) were performed to investigate potential mechanisms through which prognostic autophagy signatures regulate LUAD. Radiotherapy-resistant cell lines (A549IR and PC9IR) were established after exposure to hypo-fractionated irradiation. Ultimately, mRNA expression was validated by quantitative real-time PCR (qRT-PCR), and relative protein levels were measured in different cell lines by western blot. Results A total of 11 DERRAGs were identified in LUAD. After Cox analyses, SHC1, NAPSA, and AURKA were filtered as prognostic signatures in LUAD. Then, the risk score model was constructed using the prognostic signatures, which had a good performance in predicting the prognosis, as evidenced by receiver operating characteristics curves. Furthermore, Cox regression analyses demonstrated that risk score was deemed as an independent prognostic factor in LUAD. Moreover, GSEA and ssGSEA results revealed that prognostic RRAGs may regulate LUAD by modulating the immune microenvironment and affecting cell proliferation. The colony formation assay showed that the radiosensitivity of radiation-resistant cell lines was lower than that of primary cells. The western blot assay found that the levels of autophagy were elevated in the radiotherapy-resistant cell lines. Moreover, the expression of DERRAGs (SHC1, AURKA) was higher in the radiotherapy-resistant cells than in primary cells. Conclusion Our study explored the role of RRAGs in the prognosis of LUAD and identified three biomarkers. The findings enhanced the understanding of the relationship between radiotherapy, autophagy, and prognosis in LUAD and provided potential therapeutic targets for LUAD patients.
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Affiliation(s)
- Jingyan Gao
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Fei Lu
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
- Department of Oncology and Hematology, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe State, Mengzi, China
| | - Jiawen Yan
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Run Wang
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Yaoxiong Xia
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Li Wang
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Lan Li
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Li Chang
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
- *Correspondence: Wenhui Li, ; Li Chang,
| | - Wenhui Li
- Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China
- *Correspondence: Wenhui Li, ; Li Chang,
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17
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Xu X, Chen D, Wu X, Wang Q. A pulmonary enteric adenocarcinoma patient harboring a rare EGFR exon 19 P753S mutation: Case report and review. Front Oncol 2022; 12:988625. [PMID: 36212391 PMCID: PMC9538506 DOI: 10.3389/fonc.2022.988625] [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: 07/07/2022] [Accepted: 08/24/2022] [Indexed: 11/20/2022] Open
Abstract
Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of non–small cell lung cancer (NSCLC), accounting for about 0.6% of all primary lung adenocarcinoma. Although epidermal growth factor receptor (EGFR) mutation is common in primary lung adenocarcinoma, it is rarely reported in PEAC. This case report describes a PEAC patient with co-mutations of EGFR, Kirsten rat sarcoma viral oncogene (KRAS), and TP53, being treated with immunotherapy combined with chemotherapy. A 69-year-old man complained of cough and expectoration with bloody sputum for 2 weeks. The lung-enhanced CT scan showed a massive soft tissue shadow, about 46 × 35 mm in the lower lobe of the right lung. The neoplasm sample in the lower lobe of the right lung was obtained using CT-guided fine-needle aspiration (FNA). Immunohistochemical assays showed that the tumor was positive for CK7, CDX-2, C-MET, and villin. Gastroscopy and rectal colonoscopy had been performed respectively to exclude a diagnosis of colorectal adenocarcinoma. The patient was finally diagnosed with pulmonary intestinal adenocarcinoma. Next-generation sequencing (NGS) analysis showed a rare EGFR exon 19 missense mutation (c.2257C>T, p.P753S), KRAS exon 2 missense mutation (c.35G>T, p.G12V), and TP53 exon 5 missense mutation (c.401T>C, p.F134S). The lung-enhanced CT scan showed that the tumor shrank after four cycles of chemotherapy combined with immunotherapy. We hope that this case report can increase the understanding of this rare type of tumor and provide new molecular indications for diagnosis and individualized treatment. Furthermore, the combination of chemotherapy and immunotherapy seems to be an effective therapy for PEAC. Whether the use of immunotherapy can provide clinical benefits needs to be further explored with more samples in future studies.
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Affiliation(s)
- Xiaohu Xu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dong Chen
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiao Wu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Wang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Qi Wang,
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18
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Zuo Y, Zhong J, Bai H, Xu B, Wang Z, Li W, Chen Y, Jin S, Wang S, Wang X, Wan R, Xu J, Fei K, Han J, Yang Z, Bao H, Shao Y, Ying J, Song Q, Duan J, Wang J. Genomic and epigenomic profiles distinguish pulmonary enteric adenocarcinoma from lung metastatic colorectal cancer. EBioMedicine 2022; 82:104165. [PMID: 35901658 PMCID: PMC9334343 DOI: 10.1016/j.ebiom.2022.104165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 06/28/2022] [Accepted: 06/30/2022] [Indexed: 11/16/2022] Open
Affiliation(s)
- Ying Zuo
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jia Zhong
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Hua Bai
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Bin Xu
- Cancer center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhijie Wang
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Weihua Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yedan Chen
- Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Shi Jin
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China
| | - Shuhang Wang
- GCP Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xin Wang
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Rui Wan
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jiachen Xu
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Kailun Fei
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jiefei Han
- Department of Neuro-oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University, China
| | - Zhenlin Yang
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Hua Bao
- Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Yang Shao
- Nanjing Geneseeq Technology Inc., Nanjing, China; School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Qibin Song
- Cancer center, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Jianchun Duan
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jie Wang
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Teranishi S, Sugimoto C, Nagayama H, Segawa W, Miyasaka A, Hiro S, Maeda C, Tamura H, Masumoto N, Nagahara Y, Hirama N, Kobayashi N, Yamamoto M, Kudo M, Kaneko T. Combination of Pembrolizumab With Platinum-containing Chemotherapy for Pulmonary Enteric Adenocarcinoma. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:253-257. [PMID: 35399182 PMCID: PMC8962809 DOI: 10.21873/cdp.10102] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 01/05/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND/AIM Pulmonary enteric adeno-carcinoma (PEAC) is a rare type of non-small cell lung cancer (NSCLC), for which no established standard treatment exists. Combination therapy with the anti-programmed cell death protein 1 antibody pembrolizumab and platinum-containing chemotherapy is the standard treatment for NSCLC patients, but its effectiveness in PEAC is uncertain. CASE REPORT We present a 68-year-old man with chemotherapy-naïve advanced PEAC who responded to a combination of pembrolizumab and platinum-containing chemotherapy. CONCLUSION The number of PEAC cases is small, and no clinical trials have been conducted to determine an optimal chemotherapy regimen. In this case, we showed that pembrolizumab combined with platinum-containing chemotherapy might effectively treat PEAC.
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Affiliation(s)
- Shuhei Teranishi
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Chihiro Sugimoto
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Hirokazu Nagayama
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Wataru Segawa
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Atsushi Miyasaka
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Shuntaro Hiro
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Chihiro Maeda
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Hironori Tamura
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Nami Masumoto
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Yoshinori Nagahara
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Nobuyuki Hirama
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Nobuaki Kobayashi
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masaki Yamamoto
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Kudo
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Takeshi Kaneko
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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20
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Inoue H, Matsushima J, Kobayashi S, Sairenchi T, Hirata H, Chida M, Ota S, Ban S, Matsumura Y. Expression of nSATB2 in Neuroendocrine Carcinomas of the Lung: Frequent Immunopositivity of Large Cell Neuroendocrine Carcinoma with a Diagnostic Pitfall. Int J Surg Pathol 2021; 30:151-159. [PMID: 34913369 DOI: 10.1177/10668969211065757] [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: 11/15/2022]
Abstract
Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are both classified as lung neuroendocrine carcinoma (NEC). It has recently been reported that the special AT-rich sequence-binding protein 2 (STAB2), known as a colorectal cancer marker, is also expressed in NECs occurring in various organs including the lung. However, few studies have examined any differences of SATB2 immunopositivity between SCLC and LCNEC. We investigated SATB2 expression in 45 SCLC and 14 LCNEC cases using immunohistochemistry as well as the expression of caudal-type homeobox 2 (CDX2) and keratin (KRT) 20. The LCNEC cases were more frequently positive for SATB2 (ten out of 14, 71%) than the SCLC ones (seventeen out of 45, 38%) with a statistically significance (P = 0.035). Furthermore, two LCNEC cases were positive for CDX2 while no positive findings were observed for any SCLC cases, the difference of which, however, was not statistically significant (P = 0.053). KRT20 was negative in all LCNEC and SCLC cases. These results require our attention when we use SATB2 and CDX2 as colorectal cancer markers because their expression in pulmonary NECs can lead to a misdiagnosis that the tumor is of metastatic colorectal adenocarcinoma, especially when the patient has a past history of colorectal cancer. Analyzing the relationship between the demographic/clinical variables and the SATB2 expression in the SCLC cases, just high Brinkman index (≥ 600) was significantly related to the positivity of SATB2 (P = 0.017), which is interesting considering the strong relationship between SCLC and smoking.
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Affiliation(s)
- Hiromichi Inoue
- 26263Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Jun Matsushima
- 26263Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Satoru Kobayashi
- 26263Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | | | - Hirokuni Hirata
- 26263Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | | | - Satoshi Ota
- 37009Teine Keijinkai Hospital, Sapporo, Japan
| | - Shinichi Ban
- 26263Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Yuji Matsumura
- 26263Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
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21
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Tu LF, Sheng LY, Zhou JY, Wang XF, Wang YH, Shen Q, Shen YH. Diagnosis and treatment of primary pulmonary enteric adenocarcinoma: Report of Six cases. World J Clin Cases 2021; 9:9236-9243. [PMID: 34786410 PMCID: PMC8567515 DOI: 10.12998/wjcc.v9.i30.9236] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 06/28/2021] [Accepted: 08/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary pulmonary enteric adenocarcinoma (PEAC) is a very rare subtype of invasive adenocarcinoma, and there have been no large studies on PEAC to date. Therefore, it is necessary to obtain much more information about the clinical and pathological features, diagnosis, differential diagnosis, and treatment of PEAC.
CASE SUMMARY All clinical data of six patients with confirmed PEAC from 2013 to 2018 were collected, and data on diagnosis, differential diagnosis, and treatment of PEAC are discussed combined with all the associated literature. The mean age of six patients was 64.0 ± 5.6 (59-73) years old. Their clinical manifestations were heterogeneous, and during their disease course, there were no gastrointestinal symptoms. There was no evidence from colonoscopy or imaging studies to suggest digestive tract tumors or new metastases. The most commonly mutated gene was KRAS (50.0%), and the pathological features of the six cases were similar to those of colorectal cancer. CDX2 (83.3%) and CK7 (66.7%) had the highest positive rates upon immunohistochemical examination. In the associated literature, 252 cases were identified, and the most commonly mutated gene was KRAS (42.9%). Additionally, CDX2 (68.3%) and CK7 (85.8%) had the highest positive rates. Patients mainly received surgery, chemotherapy, and radiotherapy, immunotherapy was not included.
CONCLUSION Positive results for CDX2 and CK7 play an important role in the diagnosis and differential diagnosis of PEAC, and immunotherapy or targeted therapy focused on KRAS needs to be further studied for the treatment of PEAC.
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Affiliation(s)
- Ling-Fang Tu
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Ling-Yan Sheng
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Jian-Ying Zhou
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Xue-Fen Wang
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Yue-Hong Wang
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qian Shen
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Yi-Hong Shen
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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22
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Gong J, Fan Y, Lu H. Pulmonary enteric adenocarcinoma. Transl Oncol 2021; 14:101123. [PMID: 34000642 PMCID: PMC8141771 DOI: 10.1016/j.tranon.2021.101123] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/08/2021] [Accepted: 05/09/2021] [Indexed: 12/22/2022] Open
Abstract
Synthetically expounded the clinical characteristics of PEAC. Systematically described the differentiation of PEAC from primary lung adenocarcinoma and MCRC. Found patients with PEAC may have high frequencies of HER2 and MMR mutations. Proposed a new conjecture that patients with PEAC might benefit from anti-HER2 therapy and immune checkpoint inhibitors. Pulmonary enteric adenocarcinoma (PEAC) is an exceptionally rare subtype of non–small cell lung cancer (NSCLC). It is characterized by pathological features similar to those of colorectal adenocarcinoma. Most patients with PEAC have almost no special clinical manifestations, and it is often difficult to differentiate from metastatic colorectal adenocarcinoma (MCRC). As a special type of lung adenocarcinoma, PEAC has unique mutation expression and immune characteristics; its mutation profile shows higher Kirsten rat sarcoma viral oncogene (KRAS), human epidermal growth factor receptor-2 (HER2) , DNA mismatch repair(MMR) mutation rates, and much lower epidermal growth factor receptor (EGFR) rate. So in the future, targeted therapy may tend to be a new light in the treatment of PEAC. As for immunohistochemistry (IHC), CDX-2, villin, and CK7 are significantly positive in PEAC. This review focuses on the pathologic features, immunohistochemical examination, mutation analysis, diagnosis, treatment, and prognosis of PEAC.
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Affiliation(s)
- Jiali Gong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, PR China; Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (lung and esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, 310022, PR China
| | - Ying Fan
- Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (lung and esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, 310022, PR China; The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325035, PR China
| | - Hongyang Lu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, PR China; Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (lung and esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, 310022, PR China.
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23
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Weidemann S, Böhle JL, Contreras H, Luebke AM, Kluth M, Büscheck F, Hube-Magg C, Höflmayer D, Möller K, Fraune C, Bernreuther C, Rink M, Simon R, Menz A, Hinsch A, Lebok P, Clauditz T, Sauter G, Uhlig R, Wilczak W, Steurer S, Burandt E, Krech R, Dum D, Krech T, Marx A, Minner S. Napsin A Expression in Human Tumors and Normal Tissues. Pathol Oncol Res 2021; 27:613099. [PMID: 34257582 PMCID: PMC8262149 DOI: 10.3389/pore.2021.613099] [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: 10/01/2020] [Accepted: 02/26/2021] [Indexed: 11/25/2022]
Abstract
Background: Novel aspartic proteinase of the pepsin family A (Napsin A, TAO1/TAO2) is a functional aspartic proteinase which is involved in the maturation of prosurfactant protein B in type II pneumocytes and the lysosomal protein catabolism in renal cells. Napsin A is highly expressed in adenocarcinomas of the lung and is thus commonly used to affirm this diagnosis. However, studies have shown that other tumors can also express Napsin A. Methods: To comprehensively determine Napsin A expression in normal and tumor tissue, 11,957 samples from 115 different tumor types and subtypes as well as 500 samples of 76 different normal tissue types were evaluable by immunohistochemistry on tissue microarrays. Results: Napsin A expression was present in 16 different tumor types. Adenocarcinoma of the lung (85.6%), clear cell adenocarcinoma of the ovary (71.7%), clear cell adenocarcinoma of the endometrium (42.8%), papillary renal cell carcinoma (40.2%), clear cell (tubulo) papillary renal cell carcinoma (16.7%), endometrial serous carcinoma (9.3%), papillary thyroid carcinoma (9.3%) and clear cell renal cell carcinoma (8.2%) were among the tumors with the highest prevalence of Napsin A positivity. In papillary and clear cell renal cell carcinoma, reduced Napsin A expression was linked to adverse clinic-pathological features (p ≤ 0.03). Conclusion: This methodical approach enabled us to identify a ranking order of tumors according to their relative prevalence of Napsin A expression. The data also show that loss of Napsin A is linked to tumor dedifferentiation in renal cell carcinomas.
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Affiliation(s)
- Sören Weidemann
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jan Lukas Böhle
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Hendrina Contreras
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas M Luebke
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Franziska Büscheck
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Doris Höflmayer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Möller
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Michael Rink
- Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Rainer Krech
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - David Dum
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Andreas Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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24
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Gaydarov N, Martinelli-Kläy CP, Lombardi T. A study on the immunohistochemical expression of napsin A in oral squamous cell carcinomas, intraepithelial neoplasia, and normal oral mucosa. J Histotechnol 2021; 44:139-143. [PMID: 33876717 DOI: 10.1080/01478885.2021.1894391] [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: 10/21/2022]
Abstract
Napsin A is an aspartic proteinase expressed in some types of carcinomas, such as lung adenocarcinomas and renal cell carcinomas but rarely in squamous cell carcinomas. No specific studies have been carried out focusing on napsin A antibody expression in oral squamous cell carcinomas (OSCC). The aim of this study was to investigate the reactivity of this antibody in primary OSCC. This retrospective study included 70 OSCC cases of which 31 (44.3%) presented metastasis involvement. Patient data, including age, gender, tumor location, histological grade, regional and distant metastasis, were collected. OSCC edge epithelium with intraepithelial neoplasia and healthy oral mucosa (n = 10) were included in the analysis. Sections of lung adenocarcinomas (n = 2) were used as the positive control and an immunohistochemical assay for napsin A was performed on all cases. Napsin A expression was negative in all 70 cases of OSCC, as well as in the intraepithelial neoplasia adjacent to the carcinoma area and in healthy oral mucosa epithelium. Metastatic neck lymph nodes and distant organs were also negative for napsin A. This study shows that napsin A is consistently not expressed in oral squamous cell carcinoma, or in metastatic sites of primary OSCC, intraepithelial neoplasia, and healthy oral mucosa.
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Affiliation(s)
- Nicolay Gaydarov
- Laboratory of Oral & Maxillofacial Pathology, Oral Medicine and Oral and Maxillofacial Pathology Unit, Division of Oral Maxillofacial Surgery, Department of Surgery, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
| | - Carla P Martinelli-Kläy
- Laboratory of Oral & Maxillofacial Pathology, Oral Medicine and Oral and Maxillofacial Pathology Unit, Division of Oral Maxillofacial Surgery, Department of Surgery, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
| | - Tommaso Lombardi
- Laboratory of Oral & Maxillofacial Pathology, Oral Medicine and Oral and Maxillofacial Pathology Unit, Division of Oral Maxillofacial Surgery, Department of Surgery, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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25
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Abstract
Pulmonary enteric adenocarcinoma (PEAC) is an extremely rare type of non-small cell lung cancer (NSCLC) with a histologic pattern that mimics metastatic colorectal cancer (MCC). The main clinical symptoms in PEAC patients are dyspnoea, coughing, hemoptysis, and chest and back pain. The first article about PEAC appeared in 1991 in the form of a case report. As a variant of invasive lung carcinoma, only a small number of case reports and clinical research studies have been carried out, and the only one guidance on diagnosis and treatment is the WHO Tumor Classification book. It is important for doctors to distinguish PEAC from MCC to extend survival time and improve the quality of life. We reviewed the existing literature regarding the diagnosis, treatment, and prognosis of PEAC to provide some valuable clinical references.
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Affiliation(s)
- Haiyan Li
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Cao
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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26
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Sharifai N, Abro B, Chen JF, Zhao M, He H, Cao D. Napsin A is a highly sensitive marker for nephrogenic adenoma: an immunohistochemical study with a specificity test in genitourinary tumors. Hum Pathol 2020; 102:23-32. [PMID: 32561332 DOI: 10.1016/j.humpath.2020.05.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 05/12/2020] [Accepted: 05/31/2020] [Indexed: 11/29/2022]
Abstract
Nephrogenic adenomas are uncommon benign lesions that are typically cytologically bland, but degenerative and reactive changes may make it difficult to distinguish these lesions from malignant entities, such as urothelial carcinoma and prostatic adenocarcinoma. In this study, we explored whether napsin A, a sensitive marker for lung adenocarcinoma, may also have a role in distinguishing nephrogenic adenoma from other genitourinary lesions. Immunohistochemically, napsin A was expressed in all 43 nephrogenic adenomas (bladder: 38, prostatic urethra: 4, and ureter: 1; mean positive tumor cells: 72%, median: 80%, range: 15-100%) and showed regional variability in its expression pattern with a bias toward surface architectures (flat, papillary) compared with stromal architectures (tubular/glandular, microcystic). We also compared napsin A with other markers including PAX8, GATA3, p63, and 34BE12. Although napsin A matched PAX8 in terms of its sensitivity for nephrogenic adenoma (100%), napsin A stained a lower percentage of tumor cells than PAX8 (72% vs 99%, respectively, P = 1.0 × 10-5). P63 was negative in all nephrogenic adenomas, whereas GATA3 showed variable staining in 25 cases (58%). All 43 nephrogenic adenomas showed variable 34BE12 staining. Finally, we profiled napsin A expression among 401 genitourinary tumors on tissue microarrays (n = 308) and full tissue blocks (N = 93) and observed napsin A positivity in 37 tumors (9%), which included urothelial carcinomas with the glandular/microcystic component differentiation (in the glandular/microcystic component in 4/6), bladder adenocarcinomas (primary: 4/4 and metastatic: 3/3), urinary tract clear-cell carcinomas (primary: 8/9, metastatic uterine primary: 1/1), and some renal tumors (17/174). All 81 pure urothelial carcinomas and 53 prostatic acinar adenocarcinomas were negative for napsin A. Our study indicates that napsin A is a highly sensitive marker for nephrogenic adenoma and can serve as a useful addition in immunohistochemical panels seeking to distinguish it from pure urothelial carcinoma and prostatic acinar adenocarcinoma but not clear-cell carcinoma or urothelial carcinoma with glandular differentiation.
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Affiliation(s)
- Nima Sharifai
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63011, United States
| | - Brooj Abro
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63011, United States
| | - Jie-Fu Chen
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63011, United States
| | - Ming Zhao
- Department of Pathology, Zhejiang Provincial People's Hospital & People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, China
| | - Huiying He
- Department of Pathology, School of Basic Medical Sciences, The Third Hospital, Peking University Health Science Center, Beijing, 100191, China
| | - Dengfeng Cao
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63011, United States.
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27
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Analysis of lung biopsies using the 2015 WHO criteria and detection of sensitizing mutations--a single-institution experience of 5032 cases. Diagn Pathol 2020; 15:59. [PMID: 32429938 PMCID: PMC7236924 DOI: 10.1186/s13000-020-00975-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 05/07/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND A specialized classification for small biopsies was added to the 2015 WHO classification of lung tumors. The purpose of this study is to explore and summarize the experience of applying the newly proposed classifications and criteria to clinical practice. METHODS We used the 2015 WHO criteria to sort out 5032 small lung biopsies from a group of Chinese patients, and demonstrated their clinicopathological features, mutational status and the relationship between these factors. RESULTS The most common diagnosis was primary lung carcinoma (3130, 62.2%), among which adenocarcinoma (1421, 28.2%) was the most frequent histological type. The mutational assays using ARMS-PCR technology demonstrated that EGFR was positive in 56.1% cases(499/889, from adenocarcinoma and NSCC, favor adenocarcinoma), ALK in 5.7% cases(12/211, from NSCC, which comprised all the primary lung carcinomas except small cell carcinomas), and ROS1 in 0.9% cases(2/211, from NSCC). Another 898 NSCC specimens went through an immunohistochemical (IHC) examination for ALK (D5F3) and 38 of them were positive (4.2%). The overall mutation rate of ALK was 4.5% (50/1119). There was no significant difference between ARMS-PCR and immunohistochemistry in the positive rate of ALK mutation detection (P = 0.359). EGFR mutations (P = 0.02) and ALK mutations (P < 0.001) both decreased with an increasing patient age. Furthermore, the amount of EGFR mutations was higher in adenocarcinoma (64.1% vs 34.1%, P < 0.001) than in NSCC, favor adenocarcinoma. In contrast, ALK mutations were more common in NSCC, favor adenocarcinoma (4.2% vs 8.4%, P = 0.021). CONCLUSIONS This single-center study exhibited a large subset of small lung biopsies from a Chinese institution and demonstrated that applying the 2015 WHO classification for small lung biopsies can help predict the mutational status of primary lung carcinomas.
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28
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Smith AP, Dueber JC, Allison DB. A diagnostic review of carcinomas and sarcomas of the mediastinum: making the diagnosis on fine-needle aspiration and core needle biopsy specimens. Semin Diagn Pathol 2020; 37:187-198. [PMID: 32532552 DOI: 10.1053/j.semdp.2020.04.007] [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: 01/13/2020] [Revised: 04/14/2020] [Accepted: 04/17/2020] [Indexed: 11/11/2022]
Abstract
The mediastinum is a complex anatomic region that can pose many diagnostic challenges on fine-needle aspiration (FNA) and core needle biopsy (CNB). With the recent technological advancements in EBUS-TBNA and EUS-guided procedures, FNA/CNB is being increasingly utilized to obtain the initial and, in many cases, the only diagnosis. As a result, it is imperative to have an understanding of the pearls and pitfalls associated with both the more common and rarer malignancies that occur at this site. Although the vast majority of mediastinal malignancies encountered in routine clinical practice are metastatic carcinomas to mediastinal lymph nodes, primary tumors and tumors that directly extend into the mediastinum are also encountered. As always, a multimodal approach with clinical and radiographic correlation, a targeted IHC panel, and molecular testing when indicated are indisposable and necessary tools in the diagnostic workup of mediastinal malignancies. This review focuses on the salient diagnostic features of malignancies of epithelial and mesenchymal origin, excluding tumors of neurogenic, thymic, hematolymphoid, and germ cell origins, which are discussed in separate articles of this issue.
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Affiliation(s)
- Alexander P Smith
- Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, 800 Rose Street, MS 117, Lexington, KY 40536, USA
| | - Julie C Dueber
- Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, 800 Rose Street, MS 117, Lexington, KY 40536, USA
| | - Derek B Allison
- Department of Pathology and Laboratory Medicine, Markey Cancer Center, University of Kentucky, 800 Rose Street, MS 117, Lexington, KY 40536, USA.
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Abstract
Most commonly described as sporadic, pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare variant of invasive lung cancer recently established and recognised by the World Health Organization. This tumour is highly heterogeneous and shares several morphological features with pulmonary and colorectal adenocarcinomas. Our objective is to summarise current research on PAED, focusing on its immunohistochemical and molecular features as potential tools for differential diagnosis from colorectal cancer, as well as prognosis definition and therapeutic choice. PAED exhibits an 'entero-like' pathological morphology in more than half cases, expressing at least one of the typical immunohistochemical markers of enteric differentiation, namely CDX2, CK20 or MUC2. For this reason, this malignancy appears often indistinguishable from a colorectal cancer metastasis, making the differential diagnosis laborious. Although standard diagnostic criteria have not been established yet, in the past few years, a number of approaches have been addressed, aimed at defining specific immunohistochemical and molecular signatures. Based on previously published literature, we have collected and analysed molecular and immunohistochemical data on this rare neoplasm, and have described the state of the art on diagnostic criteria as well as major clinical and therapeutic implications.The analysis of data from 295 patients from 58 published articles allowed us to identify the most represented immunohistochemical and molecular markers, as well as major differences between Asian PAEDs and those diagnosed in European/North American countries. The innovative molecular approaches, exploring driver mutations or new gene alterations, could help to identify rare prognostic factors and guide future tailored therapeutic approaches to this rare neoplasm.
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30
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Ghanadan A, Jahanzad I, Abbasi A. Immunohistochemistry of Cancers. CANCER IMMUNOLOGY 2020:645-709. [DOI: 10.1007/978-3-030-30845-2_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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31
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Jurmeister P, Vollbrecht C, Behnke A, Frost N, Arnold A, Treue D, Rückert JC, Neudecker J, Schweizer L, Klauschen F, Horst D, Hummel M, Dietel M, von Laffert M. Next generation sequencing of lung adenocarcinoma subtypes with intestinal differentiation reveals distinct molecular signatures associated with histomorphology and therapeutic options. Lung Cancer 2019; 138:43-51. [PMID: 31634654 DOI: 10.1016/j.lungcan.2019.10.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 09/24/2019] [Accepted: 10/07/2019] [Indexed: 01/06/2023]
Abstract
OBJECTIVES We aim to provide a better understanding of the molecular landscape of primary lung adenocarcinomas with intestinal differentiation. MATERIAL AND METHODS Five invasive mucinous adenocarcinomas (IMA) and seven pulmonary enteric adenocarcinomas (PEAD) were included in this study. Furthermore, we analyzed six pulmonary colloid adenocarcinomas (CAD), including one primary tumor, one metastasis, and two sample pairs consisting of the primary colloid lung tumor and a matching metastasis and an acinar component, respectively. All samples were characterized using immunohistochemistry (TTF-1, CK7, CK20, CDX2, Ki-67, ALK and PD-L1) and a next generation sequencing panel covering 404 cancer-related genes (FoundationOne® gene panel). RESULTS AND CONCLUSION While Ki-67 expression was comparably low in IMA (range: 8-15%) and in primary CAD (range: 5-8%), we observed considerably higher proliferation rates in the non-colloid tumor compartment (16%) and metastases (72%) from CAD, as well as in the PEAD-group (36-71%). The overall tumor mutational burden was lowest in IMA (2.5 mutations per megabase), intermediate in CAD (5.8 mutations per megabase) and highest in PEAD (16.8 mutations per megabase). KRAS mutations were frequent in all three tumor subtypes, but TP53 mutations were mostly limited to PEAD. While chromosomal alterations were rare in IMA, we discovered MYC amplifications in three of four CAD. Comparing primary and metastatic CAD, we observed the acquisition of multiple mutations and chromosomal alterations. PEAD had a variety of chromosomal alterations, including two cases with RICTOR amplification. PD-L1 expression (20%, 50% and 80% of tumor cells) was limited to three PEAD samples, only. In conclusion, we provide a detailed insight into the molecular alterations across and within the different subtypes of pulmonary adenocarcinomas with intestinal differentiation. From a clinical perspective, we provide data on potential treatment strategies for patients with PEAD, including immunotherapy.
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Affiliation(s)
- Philipp Jurmeister
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany; Charité Comprehensive Cancer Center (CCCC), Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
| | - Claudia Vollbrecht
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
| | - Anke Behnke
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Nikolaj Frost
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Department of Infectious Diseases and Pneumonology, Berlin, Germany
| | - Alexander Arnold
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Denise Treue
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Jens-Carsten Rückert
- Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Jens Neudecker
- Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Leonille Schweizer
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Department of Neuropathology, Berlin, Germany
| | - Frederick Klauschen
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - David Horst
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Michael Hummel
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Manfred Dietel
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Maximilian von Laffert
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Bhatti V, Kwatra KS, Puri S, Calton N. Histopathological Spectrum and Immunohistochemical Profile of Lung Carcinomas: A 9-Year Study from a Tertiary Hospital in North India. Int J Appl Basic Med Res 2019; 9:169-175. [PMID: 31392181 PMCID: PMC6652278 DOI: 10.4103/ijabmr.ijabmr_66_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background: Lung cancer is the most common cancer worldwide and the leading cause of cancer-related death. Diagnostic bronchoscopic or percutaneous biopsies are usually small. However, judicious use of immunohistochemistry (IHC) helps in accurate subtyping, which forms the basis for molecular tests and treatment. Aim: The aim was to study the role of IHC in the diagnosis of various histological subtypes of lung cancer. Methods: This 9-year study from 2009 to 2017 included all cases diagnosed as lung carcinoma on tissue biopsies. IHC markers were selected based on histopathology, from a panel comprising CK7, CK20, CK5/6, p63, thyroid transcription factor 1 (TTF-1), napsin A, synaptophysin, chromogranin A, neuron-specific enolase, CD56, and CDX2. Metastatic cancers to the lung were excluded from the study. Results: There were 199 cases of lung carcinoma comprising squamous cell carcinoma (37.7% [n = 75]), adenocarcinoma (26.1% [n = 52]), small cell carcinoma (20.6% [n = 41]), non-small cell lung carcinoma-unclassified (10.1% [n = 20]), adenosquamous carcinoma (2.5% [n = 5]), and others (3% [n = 6]). IHC was done on 47.7% (95/199) of cases. Squamous cell carcinomas showed CK5/6 and p63 positivity in 13/13 (100%) and 12/13 (92.3%) cases, respectively. Adenocarcinomas were positive for napsin A in 12/13 (92.3%) and TTF-1 in 35/41 (85.4%) cases. Neuroendocrine markers were positive in all small cell carcinomas. Conclusion: Squamous cell carcinoma was the most common primary lung malignancy in the North Indian population, followed by adenocarcinoma and small cell carcinoma. IHC panel of TTF-1, napsin A, CK5/6, and p63 is very helpful to classify most non-small cell lung carcinomas.
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Affiliation(s)
- Vandana Bhatti
- Department of Pathology, Christian Medical College and Hospital, Ludhiana, Punjab, India
| | | | - Shivani Puri
- Department of Pathology, Christian Medical College and Hospital, Ludhiana, Punjab, India
| | - Nalini Calton
- Department of Pathology, Christian Medical College and Hospital, Ludhiana, Punjab, India
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Kuan K, Khader SN, El Hussein S. Fine-needle aspiration of lung primary adenocarcinoma with enteric differentiation. Diagn Cytopathol 2019; 47:1076-1078. [PMID: 31241853 DOI: 10.1002/dc.24264] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 05/28/2019] [Accepted: 06/05/2019] [Indexed: 11/10/2022]
Affiliation(s)
- Kevin Kuan
- The Leopold G. Koss Division of Cytopathology, Montefiore Hospital and Medical Center/Albert Einstein College of Medicine, New York, NY
| | - Samer N Khader
- The Leopold G. Koss Division of Cytopathology, Montefiore Hospital and Medical Center/Albert Einstein College of Medicine, New York, NY
| | - Siba El Hussein
- The Leopold G. Koss Division of Cytopathology, Montefiore Hospital and Medical Center/Albert Einstein College of Medicine, New York, NY
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34
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Jurmeister P, Schöler A, Arnold A, Klauschen F, Lenze D, Hummel M, Schweizer L, Bläker H, Pfitzner BM, Mamlouk S, Sers C, Denkert C, Stichel D, Frost N, Horst D, von Laffert M, Capper D. DNA methylation profiling reliably distinguishes pulmonary enteric adenocarcinoma from metastatic colorectal cancer. Mod Pathol 2019; 32:855-865. [PMID: 30723296 DOI: 10.1038/s41379-019-0207-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 12/27/2018] [Accepted: 12/29/2018] [Indexed: 12/20/2022]
Abstract
Pulmonary enteric adenocarcinoma is a rare non-small cell lung cancer subtype. It is poorly characterized and cannot be distinguished from metastatic colorectal or upper gastrointestinal adenocarcinomas by means of routine pathological methods. As DNA methylation patterns are known to be highly tissue specific, we aimed to develop a methylation-based algorithm to differentiate these entities. To this end, genome-wide methylation profiles of 600 primary pulmonary, colorectal, and upper gastrointestinal adenocarcinomas obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database were used as a reference cohort to train a machine learning algorithm. The resulting classifier correctly classified all samples from a validation cohort consisting of 680 primary pulmonary, colorectal and upper gastrointestinal adenocarcinomas, demonstrating the ability of the algorithm to reliably distinguish these three entities. We then analyzed methylation data of 15 pulmonary enteric adenocarcinomas as well as four pulmonary metastases and four primary colorectal adenocarcinomas with the algorithm. All 15 pulmonary enteric adenocarcinomas were reliably classified as primary pulmonary tumors and all four metastases as well as all four primary colorectal cancer samples were identified as colorectal adenocarcinomas. In a t-distributed stochastic neighbor embedding analysis, the pulmonary enteric adenocarcinoma samples did not form a separate methylation subclass but rather diffusely intermixed with other pulmonary cancers. Additional characterization of the pulmonary enteric adenocarcinoma series using fluorescence in situ hybridization, next-generation sequencing and copy number analysis revealed KRAS mutations in nine of 15 samples (60%) and a high number of structural chromosomal changes. Except for an unusually high rate of chromosome 20 gain (67%), the molecular data was mostly reminiscent of standard pulmonary adenocarcinomas. In conclusion, we provide sound evidence of the pulmonary origin of pulmonary enteric adenocarcinomas and in addition provide a publicly available machine learning-based algorithm to reliably distinguish these tumors from metastatic colorectal cancer.
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Affiliation(s)
- Philipp Jurmeister
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany. .,Charité Comprehensive Cancer Center (CCCC), Berlin, Germany.
| | - Anne Schöler
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
| | - Alexander Arnold
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Frederick Klauschen
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Dido Lenze
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Michael Hummel
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Leonille Schweizer
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hendrik Bläker
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Berit Maria Pfitzner
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
| | - Soulafa Mamlouk
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christine Sers
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Carsten Denkert
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Damian Stichel
- Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nikolaj Frost
- Department of Infectious Diseases and Pneumonology, Charité University Hospital Berlin, Berlin, Germany
| | - David Horst
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Maximilian von Laffert
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Pathology, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
| | - David Capper
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
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35
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Koyama J, Horiike A, Yoshizawa T, Dotsu Y, Ariyasu R, Saiki M, Sonoda T, Uchibori K, Nishikawa S, Kitazono S, Yanagitani N, Ninomiya H, Ishikawa Y, Nishio M. Correlation between thyroid transcription factor-1 expression, immune-related thyroid dysfunction, and efficacy of anti-programmed cell death protein-1 treatment in non-small cell lung cancer. J Thorac Dis 2019; 11:1919-1928. [PMID: 31285885 DOI: 10.21037/jtd.2019.04.102] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Recent studies have suggested a correlation between immune-related thyroid dysfunction (irTD) and the superior efficacy of anti-programmed cell death protein-1 (anti-PD-1) treatment in non-small cell lung cancer (NSCLC). Embryologically, the lung and thyroid are similar in origin, and thyroid transcription factor-1 (TTF-1) expresses in both organs, including NSCLC. We explored our hypothesis that TTF-1 expression in NSCLC might correlate with irTD incidence and anti-PD-1 treatment efficacy. Methods We identified 132 patients with NSCLC treated with anti-PD-1 antibody at our hospital between December 2015 and June 2017. We evaluated TTF-1 expression in tumor by immunohistochemistry using a mouse monoclonal antibody (clone 8G7G3/1, 1:100, Dako). IrTD was defined as two or more successive abnormal levels of thyroid-stimulating hormone (TSH) during anti-PD-1 treatment. We retrospectively assessed correlations between TTF-1 expression in tumor, irTD incidence, and anti-PD-1 treatment efficacy. Results Of 132 patients, 67 (51%) and 65 (49%) were positive and negative for TTF-1, respectively. We observed irTD in 19 patients (6 positives and 13 negatives for TTF-1). The incidence of irTD was 9% and 20% in TTF-1-positive and TTF-1-negative NSCLCs, respectively (P=0.086). Particularly, in non-squamous (NSQ) cell carcinomas, the irTD incidence was significantly higher in patients negative for TTF-1 (30%) than in those positive for TTF-1 (9%; P=0.010), and TTF-1 expression was identified as a significant risk factor for irTD on multivariate logistic regression analysis [odds ratio (OR), 0.18; 95% confidence interval (CI), 0.05-0.59; P=0.005]. Furthermore, longer median progression-free survival (10.3 months) was observed in patients with TTF-1-negative NSCLC with irTD compared to those with TTF-1-positive NSCLC with irTD, TTF-1-positive NSCLC without irTD, and TTF-1-negative NSCLC without irTD (4.2, 1.4, and 2.4 months, respectively). Conclusions TTF-1 expression in NSCLC might correlate with irTD and anti-PD-1 treatment efficacy.
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Affiliation(s)
- Junji Koyama
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Horiike
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takahiro Yoshizawa
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Dotsu
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Ryo Ariyasu
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masafumi Saiki
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomoaki Sonoda
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Ken Uchibori
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shingo Nishikawa
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoru Kitazono
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Noriko Yanagitani
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hironori Ninomiya
- Division of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuichi Ishikawa
- Division of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makoto Nishio
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
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Zhang J, Xiang C, Han Y, Teng H, Li X, Shao J, Zhu L, Han-Zhang H, Ye J, Yu K. Differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal carcinoma with the assistance of next-generation sequencing and immunohistochemistry. J Cancer Res Clin Oncol 2019; 145:269-279. [PMID: 30415301 DOI: 10.1007/s00432-018-2788-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 11/02/2018] [Indexed: 12/27/2022]
Abstract
PURPOSE Pulmonary enteric adenocarcinoma (PEAC), defined as tumors with an enteric component exceeding 50% and a histological morphology similar to colorectal cancer (CRC) and metastatic colorectal carcinoma (MCC), is an extremely rare primary lung adenocarcinoma, which was recently recognized by World Health Organization (WHO). Adenocarcinomas with intestinal differentiation have also been described in other anatomic sites, including paranasal sinuses, extrahepatic biliary tree, uterine and cervix, ovary. The morphologic spectrum and immunohistochemical profiles of PEAC overlap with those of colonic adenocarcinomas, the diagnosis of PEAC remains challenging. Currently, colonoscopy has to be performed to confirm the diagnosis, resulting in low compliance due to its invasiveness. Due to the rareness of PEAC, its molecular signature has not been comprehensively examined. METHODS In this study, we investigated the molecular signatures associated with PEAC and its histological counterparts, CRC and MCC using capture-based targeted sequencing. RESULTS We revealed that 12/13 (92.31%) PEAC patients harbored mutations in well-established driver genes for non-small cell lung cancer and none of them had mutations unique to CRC. Furthermore, 13/15 (86.7%) of MCC harbored mutations that are frequently seen in CRC. CONCLUSION Collectively, our study showed that PEAC, exhibiting a similar mutational profile with NSCLC, showed a distinctive signature from CRC and MCC. Furthermore, we derived a classification model, intergrading both IHC markers and genetic signature, to accurately diagnose PEAC.
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Affiliation(s)
- Jie Zhang
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Chan Xiang
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Yuchen Han
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Haohua Teng
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Xiaojing Li
- Department of Pathology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China
| | - Jinchen Shao
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Lei Zhu
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | | | - Junyi Ye
- Burning Rock Biotech, Guangzhou, 510000, China
| | - Keke Yu
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
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Abstract
The differential diagnosis of hepatic mass lesions is broad and arriving at the right diagnosis can be challenging, especially on needle biopsies. The differential diagnosis of liver tumors in children is different from adults and is beyond the scope of this review. In adults, the approach varies depending on the age, gender, and presence of background liver disease. The lesions can be divided broadly into primary and metastatic (secondary), and the primary lesions can be further divided into those of hepatocellular origin and nonhepatocellular origin. The first category consists of benign and malignant lesions arising from hepatocytes, while the second category includes biliary, mesenchymal, hematopoietic, and vascular tumors. Discussion of nonepithelial neoplasms is beyond the scope of this review. The hepatocytic lesions comprise dysplastic nodules, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma, and the differential diagnosis can be challenging requiring clinicopathological correlation and application of immunohistochemical (IHC) markers. Liver is a common site for metastasis, sometimes presenting with an unknown primary site, and proper workup is the key to arriving at the correct diagnosis. The correct diagnosis in this setting requires a systematic approach with attention to histologic features, imaging findings, clinical presentation, and judicious use of IHC markers. The list of antibodies that can be used for this purpose keeps on growing continually. It is important for pathologists to be up to date with the sensitivity and specificity of these markers and their diagnostic role and clinical implications. The purpose of this review is to outline the differential diagnosis of hepatic masses in adults and discuss an algorithmic approach to make a right diagnosis.
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Affiliation(s)
- Monika Vyas
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Dhanpat Jain
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
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38
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Pulmonary Adenocarcinoma with Enteric Differentiation Presenting with Bronchorrhea. J Thorac Oncol 2018; 12:e120-e123. [PMID: 28748820 DOI: 10.1016/j.jtho.2017.04.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Revised: 04/03/2017] [Accepted: 04/03/2017] [Indexed: 12/15/2022]
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Manucha V, Hansen JT, Gonzalez MF, Akhtar I. Role of cytology and immunochemistry in diagnosis of metastatic malignancies in the lung: A critical appraisal. Diagn Cytopathol 2018; 46:936-944. [PMID: 30353676 DOI: 10.1002/dc.24034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 06/04/2018] [Accepted: 06/07/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Lung is one of the most common sites for primary and metastatic malignancies and a challenging site to diagnose primary versus a metastatic origin of the tumor on cytology. Pathologic diagnosis of the site of origin of cancer has major implications in the management and staging purposes and may have to be followed by testing for predictive/prognostic markers. The clinical history of a known extrapulmonary primary and the radiologic findings of multiple nodules in the lung are useful in arriving at the right diagnosis but is not always available. Rarely pulmonary metastasis may be the first manifestation of an extrapulmonary tumor or may even present as a single nodule. METHOD In this study, we reviewed cytomorphologic features of tumors metastatic to the lung (2014-2017) in conjunction with immunochemistry and evaluation of needle core biopsy when available. The review of the slides was performed with an emphasis on our ability to identify the site of origin in the tumors. RESULTS We identified 47 cases of metastatic tumors in the lung diagnosed on cytology. Clinical history was available in 83% cases and with aid of immunostains, a definitive diagnosis on the origin of the tumor was made in all these cases. In the remaining 8 cases, a primary origin could only be suggested. The use of immunochemistry facilitated the diagnosis but could be misleading. CONCLUSION The approach to the diagnosis of metastatic tumors in the lung on cytology should be largely guided by the previous clinical history and comparison with previous tissue/cellular material if available.
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Affiliation(s)
- Varsha Manucha
- Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Jeffery T Hansen
- Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Maria F Gonzalez
- Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Israh Akhtar
- Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi
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Pulmonary Adenocarcinoma With Enteric Differentiation: Immunohistochemistry and Molecular Morphology. Appl Immunohistochem Mol Morphol 2018; 26:383-387. [PMID: 27753661 DOI: 10.1097/pai.0000000000000440] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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41
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Chen M, Liu P, Yan F, Xu S, Jiang Q, Pan J, He M, Shen P. Distinctive features of immunostaining and mutational load in primary pulmonary enteric adenocarcinoma: implications for differential diagnosis and immunotherapy. J Transl Med 2018; 16:81. [PMID: 29587865 PMCID: PMC5870381 DOI: 10.1186/s12967-018-1449-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 03/15/2018] [Indexed: 02/08/2023] Open
Abstract
Background Primary pulmonary enteric adenocarcinoma (PEAC) is an extremely rare variant of invasive lung cancer. It is highly heterogeneous while shares some common morphologic and immunohistochemical features with usual pulmonary adenocarcinoma (PAC) and colorectal adenocarcinoma (CRAC), making the differential diagnosis difficult. At present there are only limited studies about distinctive features of primary PEAC and the results are often inconsistent. Methods We retrospectively analyzed total 129 primary PEACs and 50 CRACs that were published since 1991 or diagnosed in our centre. Among them eight typical samples of primary PEACs and usual PACs were detected by targeted exome sequencing. Results The combination of CK7+/CDX2+ acquires high sensitivity (71.3%) and specificity (82%) in differential diagnosis of PEACs from CRAC. The primary PEACs harbor a high incidence of KRAS mutation but almost absent of EGFR mutation. Moreover, compared with usual PACs, the primary PEACs have higher nonsynonymous tumor mutation burden and more frequent MMR mutation. Conclusions The combination of CK7+/CDX2+ immunostaining and the distinctive genetic signatures, including low incidence of sensitivity genes mutations and high tumor mutation burden, is an important supplementary to the clinical differential diagnosis of primary PEACs. Our findings thus have significant implications for development of individualized treatment strategy in these patients.
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Affiliation(s)
- Ming Chen
- Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.
| | - Pu Liu
- Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Feifei Yan
- Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Suzhen Xu
- Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Qi Jiang
- Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Jingying Pan
- Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Mengye He
- Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.
| | - Peng Shen
- Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.
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42
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Inamura K, Yokouchi Y, Kobayashi M, Ninomiya H, Sakakibara R, Subat S, Nagano H, Nomura K, Okumura S, Shibutani T, Ishikawa Y. Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes. Oncotarget 2018; 8:28725-28735. [PMID: 28404926 PMCID: PMC5438686 DOI: 10.18632/oncotarget.15647] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 01/27/2017] [Indexed: 01/04/2023] Open
Abstract
TROP2 is a transmembrane glycoprotein that is overexpressed in various cancers. Emerging evidence suggests that TROP2-targeting therapies are efficacious and safe in patients with multiple prior treatments. TROP2 is a promising target for lung cancer treatment; however, little is known regarding the association of TROP2 expression with clinicopathological/molecular features, including prognosis, in lung cancer. We examined consecutive cases of adenocarcinoma, squamous cell carcinoma (SqCC), and high-grade neuroendocrine tumor (HGNET) for the membranous expression of TROP2 using immunohistochemistry. High TROP2 expression was observed in 64% (172/270) of adenocarcinomas, 75% (150/201) of SqCCs, and 18% (21/115) of HGNETs. Intriguingly, the association of TROP2 expression with mortality was dependent on the lung cancer subtype. High TROP2 expression was associated with higher lung cancer-specific mortality in adenocarcinomas [univariable hazard ratio (HR) = 1.60, 95% confidence interval (CI) = 1.07–2.44, P = 0.022)], but not in SqCCs (univariable HR = 0.79, 95% CI = 0.35–1.94, P = 0.79). In HGNETs, high TROP2 expression was associated with lower lung cancer-specific mortality in both univariable and multivariable analyses (multivariable HR = 0.13, 95% CI = 0.020–0.44, P = 0.0003). Our results suggest a differential role for TROP2 in different lung cancer subtypes.
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Affiliation(s)
- Kentaro Inamura
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | - Yusuke Yokouchi
- Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-0005, Japan
| | - Maki Kobayashi
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | - Hironori Ninomiya
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | - Rie Sakakibara
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.,Department of Integrated Pulmonology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan
| | - Sophia Subat
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | - Hiroko Nagano
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | - Kimie Nomura
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | - Sakae Okumura
- Thoracic Oncology Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
| | - Tomoko Shibutani
- Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-0005, Japan
| | - Yuichi Ishikawa
- Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
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43
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Kriegsmann M, Harms A, Longuespée R, Muley T, Winter H, Kriegsmann K, Kazdal D, Goeppert B, Pathil A, Warth A. Role of conventional immunomarkers, HNF4-α and SATB2, in the differential diagnosis of pulmonary and colorectal adenocarcinomas. Histopathology 2018; 72:997-1006. [PMID: 29243296 DOI: 10.1111/his.13455] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 12/11/2017] [Accepted: 12/15/2017] [Indexed: 12/19/2022]
Abstract
AIMS Pulmonary (ADC) and colorectal (CRC) adenocarcinomas are frequent entities in pathological routine diagnostics. Whereas the differential diagnosis is usually straightforward based on histomorphology, it can be challenging in small biopsies. In general, CDX-2, CK20, Napsin-A and TTF-1 are recommended immunohistological markers in this scenario. Hepatocyte nuclear factor 4 alpha (HNF4-α) and special AT-rich sequence-binding protein 2 (SATB2) were described recently as promising additional markers, but comprehensive large-scale data are lacking so far. Therefore, we analysed the expression of these six markers in 1021 non-small-cell lung cancers (NSCLC), including 472 ADC as well as in 80 pulmonary metastases of CRC. METHODS AND RESULTS Tissue microarrays of NSCLC and pulmonary metastases of CRC were stained for CDX-2, CK20, HNF4-α, Napsin-A, SATB2 and TTF-1 and staining results were correlated with clinicopathological variables. ADC exhibited expression of CDX-2, CK20, HNF4-α, Napsin-A, SATB2 and TTF-1 in nine (2%), 21 (4%), 17 (4%), 345 (73%), 35 (7%) and 408 (86%) samples, while 80 CRC were positive in 79 (99%), 74 (93%), 77 (96%), no (0%), 78 (98%) and five (6%) cases, respectively. CONCLUSIONS In addition to conventional immunomarkers, HNF4-α and particularly SATB2 may be helpful in the differential diagnosis of pulmonary ADC and metastases of CRC.
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Affiliation(s)
- Mark Kriegsmann
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Alexander Harms
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.,Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research, Heidelberg, Germany
| | - Rémi Longuespée
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Muley
- Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research, Heidelberg, Germany.,Translational Research Unit, Thoraxklinik at Heidelberg University, Heidelberg, Germany
| | - Hauke Winter
- Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research, Heidelberg, Germany.,Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, Heidelberg, Germany
| | - Katharina Kriegsmann
- Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Daniel Kazdal
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.,Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research, Heidelberg, Germany
| | - Benjamin Goeppert
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Anita Pathil
- Department of Internal Medicine IV, Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
| | - Arne Warth
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.,Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research, Heidelberg, Germany
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44
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Miyaoka M, Hatanaka K, Iwazaki M, Nakamura N. CK7/CK20 Double-Negative Pulmonary Enteric Adenocarcinoma With Histopathological Evaluation of Transformation Zone Between Enteric Adenocarcinoma and Conventional Pulmonary Adenocarcinoma. Int J Surg Pathol 2018; 26:464-468. [PMID: 29411669 DOI: 10.1177/1066896918756737] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We report a rare case of pulmonary enteric adenocarcinoma (PEA) exhibiting a immunohistochemical feature of CK7/CK20 double-negativity by evaluating the transformation zone between PEA and conventional pulmonary adenocarcinoma (CPA). A 75-year-old man was found to have a mass, 40 mm in diameter, in the right lower lobe on chest computed tomography, and underwent right lower lobectomy. Histologically, the tumor was composed of a PEA and CPA component. The dominant PEA component had medium to large complex glands with tall columnar cells with eosinophilic cytoplasm and brush-border. The CPA component comprised small to medium glands with cuboidal cells. Moreover, intermediate glands (INT), which had cuboidal to tall columnar cells, with morphological features between PEA and CPA, was also observed in the transformation area. Immunohistochemically, the PEA component was negative for CK7, CK20, and TTF-1, and positive for CDX2 and SATB2 (weak): the CPA component was negative for CK20, CDX2, and SATB2, and positive for CK7 and TTF-1: the INT were negative for SATB2, with intermingled positive signals for CK7, CK20, TTF-1, and CDX2. The final diagnosis was PEA based on the CPA component and not colorectal carcinoma. To distinguish CK7-negative PEA from metastatic colorectal carcinoma, careful examination for a CPA component is very useful along with clinical information. There are no reports that discuss about process of oncogenesis, de novo sequence or transformation from CPA of PEA. This is the first reported case of CK7/CK20 double-negative PEA, with analysis of the transformation zone between PEA and CPA components.
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Affiliation(s)
- Masashi Miyaoka
- 1 Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | | | | | - Naoya Nakamura
- 1 Tokai University School of Medicine, Isehara, Kanagawa, Japan
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45
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Shannon VR, Nanda AS, Middleton LP, Faiz SA. Pulmonary Mucinous Cystadenocarcinoma Presenting as Extensive Multifocal Cystic Lesions. Am J Respir Crit Care Med 2017; 195:1267-1268. [PMID: 28199793 DOI: 10.1164/rccm.201610-2106im] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
| | - Amit S Nanda
- 2 University of Missouri at Kansas City School of Medicine, Kansas City, Missouri
| | - Lavinia P Middleton
- 3 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
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46
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Bae JM, Kim JH, Park JH, Park HE, Cho NY, Kang GH. Clinicopathological and molecular implications of aberrant thyroid transcription factor-1 expression in colorectal carcinomas: an immunohistochemical analysis of 1319 cases using three different antibody clones. Histopathology 2017; 72:423-432. [DOI: 10.1111/his.13398] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 09/12/2017] [Indexed: 11/28/2022]
Affiliation(s)
- Jeong Mo Bae
- Department of Pathology; Seoul National University Hospital; Seoul National University College of Medicine; Seoul Korea
| | - Jung Ho Kim
- Department of Pathology; Seoul National University Hospital; Seoul National University College of Medicine; Seoul Korea
| | - Jeong Hwan Park
- Department of Pathology; SMG-SNU Boramae Medical Centre; Seoul Korea
| | - Hye Eun Park
- Department of Pathology; Seoul National University Hospital; Seoul National University College of Medicine; Seoul Korea
| | - Nam-Yun Cho
- Laboratory of Epigenetics; Cancer Research Institute; Seoul National University College of Medicine; Seoul Korea
| | - Gyeong Hoon Kang
- Department of Pathology; Seoul National University Hospital; Seoul National University College of Medicine; Seoul Korea
- Laboratory of Epigenetics; Cancer Research Institute; Seoul National University College of Medicine; Seoul Korea
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47
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Muto M, Inamura K, Ozawa N, Endo T, Masuda H, Yonese J, Ishikawa Y. Skene's gland adenocarcinoma with intestinal differentiation: A case report and literature review. Pathol Int 2017; 67:575-579. [DOI: 10.1111/pin.12571] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 07/26/2017] [Indexed: 11/28/2022]
Affiliation(s)
- Mariko Muto
- Division of Pathology; The Cancer Institute; Department of Pathology; The Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | - Kentaro Inamura
- Division of Pathology; The Cancer Institute; Department of Pathology; The Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | - Naoko Ozawa
- Division of Pathology; The Cancer Institute; Department of Pathology; The Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | - Takashi Endo
- Division of Pathology; The Cancer Institute; Department of Pathology; The Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | - Hitoshi Masuda
- Department of Urology; The Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | - Junji Yonese
- Department of Urology; The Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | - Yuichi Ishikawa
- Division of Pathology; The Cancer Institute; Department of Pathology; The Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
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48
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Matsubara D, Soda M, Yoshimoto T, Amano Y, Sakuma Y, Yamato A, Ueno T, Kojima S, Shibano T, Hosono Y, Kawazu M, Yamashita Y, Endo S, Hagiwara K, Fukayama M, Takahashi T, Mano H, Niki T. Inactivating mutations and hypermethylation of the NKX2-1/TTF-1 gene in non-terminal respiratory unit-type lung adenocarcinomas. Cancer Sci 2017; 108:1888-1896. [PMID: 28677170 PMCID: PMC5581515 DOI: 10.1111/cas.13313] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 07/03/2017] [Accepted: 07/03/2017] [Indexed: 12/25/2022] Open
Abstract
The major driver mutations of lung cancer, EGFR mutations and EML4-ALK fusion, are mainly detected in terminal respiratory unit (TRU)-type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non-TRU-type lung cancer, we carried out whole-exome sequencing on 43 non-TRU-type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX2-1/TTF-1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort. Eight NKX2-1/TTF-1 mutations (five frameshift, two nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1/TTF-1 mutations (one missense and one frameshift). Functional assays with the NK2 homeobox 1 (NKX2-1)/thyroid transcription factor 1 (TTF-1) mutants revealed that none of them retain the activity as a transcriptional factor. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1/TTF-1 mutations (five cases), as well as one enteric and one acinar adenocarcinoma. Immunohistochemistry showed that the cohort was largely divided into TTF-1-postive/hepatocyte nuclear factor 4-α (HNF4-α)-negative and TTF-1-negative/HNF4-α-positive groups. NKX2-1/TTF-1 mutations were exclusively found in the latter, in which the gastrointestinal markers, mucin 5AC and cytokeratin 20, were frequently expressed. Bisulfite sequencing revealed that the NKX2-1/TTF-1 gene body was highly methylated in NKX2-1/TTF-1-negative cases, including those without the NKX2-1/TTF-1 mutations. The genetic or epigenetic inactivation of NKX2-1/TTF-1 may play an essential role in the development and aberrant differentiation of non-TRU-type lung adenocarcinomas.
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Affiliation(s)
- Daisuke Matsubara
- Division of Integrative PathologyJichi Medical UniversityShimotsukeshiJapan
| | - Manabu Soda
- Department of Cellular SignalingGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Taichiro Yoshimoto
- Division of Integrative PathologyJichi Medical UniversityShimotsukeshiJapan
| | - Yusuke Amano
- Division of Integrative PathologyJichi Medical UniversityShimotsukeshiJapan
| | - Yuji Sakuma
- Division of Integrative PathologyJichi Medical UniversityShimotsukeshiJapan
| | - Azusa Yamato
- Department of Cellular SignalingGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Toshihide Ueno
- Department of Cellular SignalingGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Shinya Kojima
- Department of Cellular SignalingGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Tomoki Shibano
- Division of Thoracic SurgeryJichi Medical UniversityShimotsukeshiJapan
| | - Yasuyuki Hosono
- Division of Molecular CarcinogenesisCenter for Neurological Diseases and CancerNagoya University Graduate School of MedicineNagoyaJapan
| | - Masahito Kawazu
- Department of Medical GenomicsGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Yoshihiro Yamashita
- Department of Cellular SignalingGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Shunsuke Endo
- Division of Thoracic SurgeryJichi Medical UniversityShimotsukeshiJapan
| | - Koichi Hagiwara
- Division of Respiratory MedicineJichi Medical UniversityShimotsukeshiJapan
| | - Masashi Fukayama
- Department of PathologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Takashi Takahashi
- Division of Molecular CarcinogenesisCenter for Neurological Diseases and CancerNagoya University Graduate School of MedicineNagoyaJapan
| | - Hiroyuki Mano
- Department of Cellular SignalingGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Toshiro Niki
- Division of Integrative PathologyJichi Medical UniversityShimotsukeshiJapan
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49
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Zhao L, Huang S, Liu J, Zhao J, Li Q, Wang HQ. Clinicopathological, radiographic, and oncogenic features of primary pulmonary enteric adenocarcinoma in comparison with invasive adenocarcinoma in resection specimens. Medicine (Baltimore) 2017; 96:e8153. [PMID: 28953659 PMCID: PMC5626302 DOI: 10.1097/md.0000000000008153] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/31/2017] [Accepted: 09/01/2017] [Indexed: 12/13/2022] Open
Abstract
Primary pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of primary lung adenocarcinoma. However, it is not known whether there are any distinctive clinical or molecular features.PEACs were retrospectively identified in 28 patients from July 2014 to June 2016. We compared the clinicopathological, radiographic, and oncogenic characteristics of PEAC and primary pulmonary invasive adenocarcinoma (IAC).A total of 28 PEAC patients and 92 IAC patients were compared. PEAC occurred more frequently in males (P = .008), in older patients (P = .041), in those with larger lesions (P = .001), and in those in a more advanced stage (P = .011). Radiologically, PEAC patients had larger lesions (P = .025) and more solid (P = .006); however, there were no statistically significant differences in lobulation, spiculation, pleural indentation, pleural effusion, and lymphadenopathy between PEAC and IAC. PEAC had higher values of carcinoembryonic antigen (P = .008) and carbohydrate antigen 19-9 (P < .001) than IAC. PEAC had a higher incidence (40% vs 63%, P < .001) of Kristen rat sarcoma viral oncogene homolog (KRAS) mutations and a lower incidence (10.71% vs 3.3%, P < .001) of epidermal growth factor receptor (EGFR) mutations. Villin may be a useful marker in the differential diagnosis of PEAC. KRAS mutations occurred more frequently in PEACs, which are cytokeratin 7-negative (P = .032). EGFR mutation rates were higher in PEACs, which are cytokeratin 20- and caudal type homeobox transcription factor 2-negative (P = .041).PEAC is a rare and heterogeneous nonsmall-cell lung cancer subgroup with distinctive clinicopathological, radiographic, and molecular features. These results need to be further confirmed in future studies.
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50
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Inamura K. Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification. Front Oncol 2017; 7:193. [PMID: 28894699 PMCID: PMC5581350 DOI: 10.3389/fonc.2017.00193] [Citation(s) in RCA: 304] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 08/11/2017] [Indexed: 12/12/2022] Open
Abstract
Lung cancer is the leading cause of cancer-related death worldwide due to late diagnoses and limited treatment interventions. Recently, comprehensive molecular profiles of lung cancer have been identified. These novel characteristics have enhanced the understanding of the molecular pathology of lung cancer. The identification of driver genetic alterations and potential molecular targets has resulted in molecular-targeted therapies for an increasing number of lung cancer patients. Thus, the histopathological classification of lung cancer was modified in accordance with the increased understanding of molecular profiles. This review focuses on recent developments in the molecular profiling of lung cancer and provides perspectives on updated diagnostic concepts in the new 2015 WHO classification. The WHO classification will require additional revisions to allow for reliable, clinically meaningful tumor diagnoses as we gain a better understanding of the molecular characteristics of lung cancer.
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Affiliation(s)
- Kentaro Inamura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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