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Wang QQ, Li YM, Qin G, Liu F, Xu YY. Primary malignant melanoma of the esophagus: A case report. World J Clin Cases 2023; 11:1426-1433. [PMID: 36926119 PMCID: PMC10013115 DOI: 10.12998/wjcc.v11.i6.1426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 01/07/2023] [Accepted: 02/07/2023] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease whose clinical and molecular pathological features, origin and pathogenesis, diagnosis and treatment have not been elucidated.
CASE SUMMARY In this paper, we report a case of a 73-year-old male with PMME. The patient complained of progressive dysphagia accompanied by substantial weight loss. Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach. Histopathological biopsy revealed melanocytes in the esophageal mucosa. Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs, such as the skin. Through this case report and literature review, we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathogenesis as well as cutting-edge therapeutic advances.
CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis. Clinicians should raise their awareness and be able to identify early lesions.
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Affiliation(s)
- Qian-Qian Wang
- Department of Gastroenterology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Yan-Mei Li
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Geng Qin
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Fang Liu
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Ying-Ying Xu
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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Cazzato G, Cascardi E, Colagrande A, Lettini T, Resta L, Bizzoca C, Arezzo F, Loizzi V, Dellino M, Cormio G, Casatta N, Lupo C, Scillimati A, Scacco S, Parente P, Lospalluti L, Ingravallo G. The Thousand Faces of Malignant Melanoma: A Systematic Review of the Primary Malignant Melanoma of the Esophagus. Cancers (Basel) 2022; 14:3725. [PMID: 35954389 PMCID: PMC9367585 DOI: 10.3390/cancers14153725] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/27/2022] [Accepted: 07/28/2022] [Indexed: 02/01/2023] Open
Abstract
Primary Malignant Melanoma of the Esophagus (PMME) is an extremely rare cancer of the esophagus, accounting for 0.1−0.8% of all oro-esophageal cancers and <0.05% of all melanoma subtypes, with an estimated incidence of 0.0036 cases per million/year. We conduct a careful analysis of the literature starting from 1906 to the beginning of 2022, searching the PubMed, Science.gov, Scopus and Web of Science (WoS) databases. A total of 457 records were initially identified in the literature search, of which 17 were duplicates. After screening for eligibility and inclusion criteria, 303 publications were ultimately included, related to 347 patients with PMME. PMME represents a very rare entity whose very existence has been the subject of debate for a long time. Over time, an increasing number of cases have been reported in the literature, leading to an increase in knowledge and laying the foundations for a discussion on the treatment of this pathology, which still remains largely represented by surgery. In recent times, the possibility of discovering greater mutations in gene hotspots has made it possible to develop new therapeutic strategies of which nivolumab is an example. Future studies with large case series, with clinicopathological and molecular data, will be necessary to improve the outcome of patients with PMME.
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Affiliation(s)
- Gerardo Cazzato
- Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.C.); (T.L.); (L.R.); (G.I.)
| | - Eliano Cascardi
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy;
- Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, Str. Provinciale 142 lm 3.95, 10060 Candiolo, Italy
| | - Anna Colagrande
- Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.C.); (T.L.); (L.R.); (G.I.)
| | - Teresa Lettini
- Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.C.); (T.L.); (L.R.); (G.I.)
| | - Leonardo Resta
- Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.C.); (T.L.); (L.R.); (G.I.)
| | - Cinzia Bizzoca
- Section of General Surgery, Azienda Ospedaliero-Universitaria Policlinico di Bari, 70124 Bari, Italy;
| | - Francesca Arezzo
- Section of Gynecology and Obstetrics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (F.A.); (V.L.); (M.D.)
| | - Vera Loizzi
- Section of Gynecology and Obstetrics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (F.A.); (V.L.); (M.D.)
| | - Miriam Dellino
- Section of Gynecology and Obstetrics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (F.A.); (V.L.); (M.D.)
| | - Gennaro Cormio
- Oncology Unit IRCSS Istituto Tumori “Giovanni Paolo II”, Department of Interdisciplinary Medicine (DIM), University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Nadia Casatta
- Innovation Department, Diapath S.p.A., Via Savoldini n.71, 24057 Martinengo, Italy; (N.C.); (C.L.)
| | - Carmelo Lupo
- Innovation Department, Diapath S.p.A., Via Savoldini n.71, 24057 Martinengo, Italy; (N.C.); (C.L.)
| | - Antonio Scillimati
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Salvatore Scacco
- Department of Basic Medical Sciences and Neurosciences, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy;
| | - Lucia Lospalluti
- Section of Dermatology and Venereology, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Giuseppe Ingravallo
- Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.C.); (T.L.); (L.R.); (G.I.)
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Chu YM, Hung CS, Huang CS. Primary malignant melanoma of the esophagogastric junction: A case report. Medicine (Baltimore) 2021; 100:e26467. [PMID: 34160452 PMCID: PMC8238344 DOI: 10.1097/md.0000000000026467] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/07/2021] [Indexed: 01/04/2023] Open
Abstract
RATIONALE Most gastrointestinal melanomas are metastatic from an oculocutaneous primary lesion; however, primary gastrointestinal melanomas have been found in all levels of the gastrointestinal tract. We present the case of Primary malignant melanoma of the esophagus and discuss the diagnostic methods, differentiation from metastatic lesions and treatment options. PATIENT CONCERNS A 78-year-old male patient presented with fresh blood vomiting and tarry stools for 1 day. DIAGNOSES Esophagogastroduodenoscopy of this patient revealed a tumor ∼4 cm in size at the cardia side of the esophagogastric junction with dark-red and gray pigmentation. Immunohistochemical stains of the biopsy specimens were positive for S-100 and HMB-45, which are specific markers of melanoma. INTERVENTIONS Laparotomy with proximal gastrectomy was performed by the surgeon. Histological examination of the surgical specimen revealed the tumor arose from the distal esophagus with invasion of the proximal stomach. Primary malignant melanoma of the esophagus was diagnosed after a full skin and ophthalmic examination and positron emission tomography, which revealed no lesions elsewhere in the body. OUTCOMES No tumor recurrence was noted at the 1-year follow-up. LESSONS Primary malignant melanoma of the esophagus is an extremely rare but highly aggressive tumor. The special pattern of pigmentation should be recognized while performing endoscopy. Early detection and radical resection of the tumor are critical to ensure favorable outcomes.
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Affiliation(s)
- Yu-Ming Chu
- Division of Digestive Medicine, Department of Internal Medicine, Cathay General Hospital
| | - Chih-Sheng Hung
- Division of Digestive Medicine, Department of Internal Medicine, Cathay General Hospital
- School of Medicine, Fu-Jen Catholic University, New Taipei City
| | - Ching-Shui Huang
- Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei City, Taiwan
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Wang S, Sun S, Liu X, Ge N, Wang G, Guo J, Liu W, Hu J. Endoscopic diagnosis of gastrointestinal melanoma. Scand J Gastroenterol 2020; 55:330-337. [PMID: 32191553 DOI: 10.1080/00365521.2020.1734074] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Background: Gastrointestinal (GI) melanoma can be diagnosed by endoscopy combined with biopsy and subsequent pathological examination. However, the disease may be misdiagnosed due to the limited awareness of GI melanoma.Objective: We aimed to describe characteristics of GI melanoma that can be detected by endoscopy and endoscopic ultrasound (EUS).Methods: We retrospectively analyzed patients with GI melanoma diagnosed by endoscopic biopsy or postoperative pathology between August 2008 and January 2017. Images of endoscopic examinations, including endoscopy and EUS, were reviewed to characterize GI melanomas.Results: A total of 21 patients (9 males, 12 females) with GI melanoma were enrolled in this study. Several types of melanoma were identified: anorectal melanoma (n = 15), esophageal melanoma (n = 3), gastric melanoma (n = 2), and melanoma of the small intestine (n = 1). EUS was performed for one case of esophageal melanoma, one case of gastric melanoma, and seven cases of anorectal melanoma.Conclusions: GI melanoma is a rare disease. Most GI melanomas showed typical endoscopic manifestations, including black plaques. EUS is a reliable tool for evaluating the depth of infiltration of GI melanoma.
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Affiliation(s)
- Sheng Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Siyu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Xiang Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Nan Ge
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Guoxin Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Jintao Guo
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Wen Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Jinlong Hu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
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Wang X, Kong Y, Chi Z, Sheng X, Cui C, Mao L, Lian B, Tang B, Yan X, Si L, Guo J. Primary malignant melanoma of the esophagus: A retrospective analysis of clinical features, management, and survival of 76 patients. Thorac Cancer 2019; 10:950-956. [PMID: 30864295 PMCID: PMC6449256 DOI: 10.1111/1759-7714.13034] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 02/13/2019] [Accepted: 02/14/2019] [Indexed: 12/13/2022] Open
Abstract
Background Primary malignant melanoma of the esophagus (PMME) is rare. Patients with advanced melanoma of esophageal origin tend to have lower response rates to traditional therapies than those with other melanomas. We report our experience of 12 patients with PMME administered PD‐1 inhibitors. Methods This is a retrospective analysis of the clinical data of 76 patients with PMME who attended Peking University Cancer Hospital between January 2008 and September 2017. Objective response rates (ORRs) and progression‐free survival (PFS) were assessed. Results The 76 PMMEs were classified as unresectable or metastatic. The patients were allocated to three cohorts according to their treatment: chemotherapy (C: 46 patients), targeted therapy (T: 2 patients), and PD‐1 inhibitors (IT: 12 patients). The PFS in the C cohort was three months with a limited ORR of 10.9%. In the IT cohort, seven patients (75.0%) achieved a partial response and three had stable disease for 4+ months. The median PFS in the IT cohort was not reached and the mean was 15.6 months, which was much longer than in cohort C (P < 0.001). Conclusion Although this cohort of patients was small, it is the largest series investigated thus far. To the best of our knowledge, this is the first report of the outcomes of advanced PMMEs treated with PD‐1 inhibitors. Dramatic responses can occur in patients with advanced PMMEs.
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Affiliation(s)
- Xuan Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Yan Kong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Zhihong Chi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Xinan Sheng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Chuanliang Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Lili Mao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Bin Lian
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Bixia Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Xieqiao Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Lu Si
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
| | - Jun Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China
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Intraepithelial Melanoma in the Stomach After Treatment With Immune Checkpoint Blockade Therapy. Am J Dermatopathol 2018; 39:e116-e118. [PMID: 28248716 DOI: 10.1097/dad.0000000000000859] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Melanoma is the most common tumor to metastasize to the gastrointestinal tract, commonly affecting the small intestine, colon, and anorectum. Primary mucosal melanoma can arise in any gastrointestinal site, most frequently affecting anorectal mucosa. Melanoma involving the gastric mucosa, specifically, is exceedingly rare and carries a poor prognosis with a median survival of 5 months. The presence of atypical melanocytes exclusively within gastric epithelium has not been previously described. We report a case of a 52-year-old man with widespread BRAFV600E mutant metastatic melanoma who was referred to our institution for immune checkpoint antibody-blockade therapy. The patient had previously been treated with BRAF inhibitors, and despite initial response to therapy, developed resistance leading to disease progression and multiorgan involvement including the liver, spleen, and axial skeleton. Immune checkpoint antibody blockade with ipilimumab and pembrolizumab has been shown to induce significant tumor regression in patients with melanoma by upregulating T-cell activity and removing the natural check on the host immune response. After his first dose of combination therapy, the patient underwent an upper gastrointestinal tract endoscopy for severe nausea and was found to have 2 pigmented lesions within the gastric body, one of which was biopsied. The biopsy showed gastric body-fundic type mucosa with melanophages and scattered atypical intraepithelial melanocytes within the lamina propria, which were strongly positive for S100, HMB45, SOX10, and MITF. A Fontana-Masson silver stain was performed for confirmation. The finding of predominantly atypical intraepithelial melanocytes associated with melanin pigment was interpreted as metastatic melanoma to the stomach with some regression in response to immune checkpoint blockade therapy.
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Li J, Yan S, Liu Z, Zhou Y, Pan Y, Yuan W, Liu M, Tan Q, Tian G, Dong B, Cai H, Wu N, Ke Y. Multiregional Sequencing Reveals Genomic Alterations and Clonal Dynamics in Primary Malignant Melanoma of the Esophagus. Cancer Res 2017; 78:338-347. [PMID: 28972077 DOI: 10.1158/0008-5472.can-17-0938] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 07/28/2017] [Accepted: 09/18/2017] [Indexed: 11/16/2022]
Abstract
Primary malignant melanoma of the esophagus (PMME) is a rare and aggressive disease with high tendency of metastasis. To characterize the genetic basis and intratumor heterogeneity of PMME, we performed multiregion exome sequencing and whole genome SNP array genotyping of 12 samples obtained from a patient with PMME. High intratumor heterogeneity was observed in both somatic mutation and copy-number alteration levels. Nine geographically separate samples including two normal samples were clonally related and followed a branched evolution model. Most putative oncogenic drivers such as BRAF and KRAS mutations as well as CDKN2A biallelic inactivation were observed in trunk clones, whereas clinically actionable mutations such as PIK3CA and JAK1 mutations were detected in branch clones. Ancestor tumor clones evolved into three subclonal clades: clade1 fostered metastatic subclones that carried metastatic features of PIK3CA and ARHGAP26 point mutations as well as chr13 arm-level deletion, clade2 owned branch-specific JAK1 mutations and PTEN deletion, and clade3 was found in two vertical distribution samples below the primary tumor area, highlighting the fact that it is possible for PMME to disseminate by the submucosal longitudinal lymphatic route at an early stage of metastasis. These findings facilitate interpretation of the genetic essence of this rare melanoma subtype as well as the pattern of cancer evolution, thus reinforcing the therapeutic challenges associated with PMME.Significance: This study highlights the use of multiregion exome sequencing and whole genome SNP array genotyping to comprehensively characterize the genetic landscape of a rare type of esophogeal melanoma. Cancer Res; 78(2); 338-47. ©2017 AACR.
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Affiliation(s)
- Jingjing Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China
| | - Shi Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhen Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yaqi Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China
| | - WenQin Yuan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China
| | - Mengfei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China
| | - Qin Tan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China
| | | | - Bin Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Lab, Peking University Cancer Hospital and Institute, Beijing, China
| | - Hong Cai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China
| | - Nan Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China.
| | - Yang Ke
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing, China.
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