PMID- 30885149 OWN - NLM STAT- MEDLINE DCOM- 20190718 LR - 20200225 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 19 IP - 1 DP - 2019 Mar 18 TI - Increased MET gene copy number negatively affects the survival of esophageal squamous cell carcinoma patients. PG - 240 LID - 10.1186/s12885-019-5450-6 [doi] LID - 240 AB - BACKGROUNDS: Since Mesenchymal epithelial transition (MET) amplification has been regarded as a potential treatment target, the knowledge of its prevalence and prognostic importance is crucial. However, its clinical pathologic characteristics are not well known in esophageal squamous cell carcinoma (ESCC). METHODS: We investigated MET gene status with fluorescence in situ hybridization (FISH) assay in 495 ESCC cases using tissue microarrays. Prognostic significance as well as correlations with various clinicopathological parameters was evaluated. RESULTS: Among 495 patients, 28 (5.7%) cases were MET FISH positive, including 5 cases (1%) with true gene amplification. There were no statistically significant associations between MET FISH-positivity and clinicopathologic characteristics. A significantly poorer prognosis was observed in 28 patients with MET FISH-positivity (disease free survival/DFS, P < 0.001 and overall survival/OS, P = 0.001). Multivariate analysis revealed MET FISH-positivity was an independent prognostic factor for DFS (hazard ratio/HR, 1.953; 95% confidence interval/CI, 1.271-2.999; P = 0.002) and OS (HR, 1.926; 95% CI, 1.243-2.983; P = 0.003). MET FISH-positivity was associated with DFS (P = 0.022 and 0.020) and OS (P = 0.046 and 0.024) both in stage I-II ESCC and in stage III-IVa ESCC. No statistical significance (DFS, P = 0.492 and OS, P = 0.344) was detected between stage I-II ESCC with MET FISH-positivity and stage III-IVa ESCC with FISH-negativity. CONCLUSIONS: Increased MET gene copy number is an independent prognostic factor in ESCC, and ESCC might have potentially been up-staged by increased MET gene copy number. The results indicate that increased MET gene copy number is a very promising parameter, in clinical therapy and follow-up plans. FAU - Wang, Yanqiu AU - Wang Y AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Jiang, Zhengzeng AU - Jiang Z AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Xu, Chen AU - Xu C AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Wang, Hao AU - Wang H AD - Department of Thoracic surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Tan, Lijie AU - Tan L AD - Department of Thoracic surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Su, Jieakesu AU - Su J AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Wang, Xin AU - Wang X AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Jiang, Dongxian AU - Jiang D AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. FAU - Hou, Yingyong AU - Hou Y AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. houyingyong@aliyun.com. AD - Department of Pathology, School of Basic Medical Sciences & Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. houyingyong@aliyun.com. AD - Department of Pathology, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201700, People's Republic of China. houyingyong@aliyun.com. FAU - Song, Qi AU - Song Q AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. qisong725@gmail.com. LA - eng GR - 18ZR1406800/Natural Science Foundation of Shanghai (CN)/ GR - 81702372/National Natural Science Foundation of China/ GR - 2015ZB0201/Foundation of Shanghai Municipal Commission of Health and Family Planning (CN)/ PT - Journal Article DEP - 20190318 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Disease-Free Survival MH - Esophageal Neoplasms/genetics/*mortality/pathology MH - Esophageal Squamous Cell Carcinoma/genetics/*mortality/pathology MH - Esophagus/pathology MH - Female MH - *Gene Amplification MH - Gene Dosage MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Prognosis MH - Proto-Oncogene Proteins c-met/*genetics MH - Retrospective Studies MH - Survival Analysis MH - Tissue Array Analysis PMC - PMC6421677 OTO - NOTNLM OT - Clinical stage OT - Esophageal squamous cell carcinoma (ESCC) OT - Fluorescence in situ hybridization (FISH) OT - Increased MET gene copy number OT - Prognosis COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Written informed consent was obtained from all patients, and the study was approved by the ethical committee of the Zhongshan Hospital, in accordance with the ethical standards of the World Medical Association Declaration of Helsinki. The authors declare no competing financial interests. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/03/20 06:00 MHDA- 2019/07/19 06:00 PMCR- 2019/03/18 CRDT- 2019/03/20 06:00 PHST- 2018/10/20 00:00 [received] PHST- 2019/03/11 00:00 [accepted] PHST- 2019/03/20 06:00 [entrez] PHST- 2019/03/20 06:00 [pubmed] PHST- 2019/07/19 06:00 [medline] PHST- 2019/03/18 00:00 [pmc-release] AID - 10.1186/s12885-019-5450-6 [pii] AID - 5450 [pii] AID - 10.1186/s12885-019-5450-6 [doi] PST - epublish SO - BMC Cancer. 2019 Mar 18;19(1):240. doi: 10.1186/s12885-019-5450-6.