PMID- 25886066 OWN - NLM STAT- MEDLINE DCOM- 20160128 LR - 20240322 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 15 DP - 2015 Feb 6 TI - MET FISH-positive status predicts short progression-free survival and overall survival after gefitinib treatment in lung adenocarcinoma with EGFR mutation. PG - 31 LID - 10.1186/s12885-015-1019-1 [doi] LID - 31 AB - BACKGROUND: Lung adenocarcinoma patients with EGFR gene mutations have shown a dramatic response to gefitinib. However, drug resistance eventually emerges which limits the mean duration of response. With that in view, we examined the correlations between MET gene status as assessed by fluorescence in situ hybridization (FISH) with overall survival (OS) and progression-free survival (PFS) in adenocarcinoma patients with EGFR gene mutations who had received gefitinib therapy. METHODS: We evaluated 35 lung cancer samples with EGFR mutation from adenocarcinoma patients who had received gefitinib. Gene copy numbers (GCNs) and amplification of MET gene before gefitinib therapy was examined by FISH. MET protein expression was also evaluated by immunohistochemistry (IHC). RESULTS: FISH assessment showed that of the 35 adenocarcinoma samples, 10 patients (29%) exhibited high polysomy (5 copies<==mean MET per cell) and 1 patient (3%) exhibited amplification (2<==MET gene (red)/CEP7q (green) per cell). IHC evaluation of MET protein expression could not confirm MET high polysomy status. The Eleven patients with MET FISH positivity had significantly shorter progression-free survival (PFS) and overall survival (OS) than the 24 patients who were MET FISH-negative (PFS: p = 0.001 and OS: p = 0.03). Median PFS and OS with MET FISH-positivity were 7.6 months and 16.8 months, respectively, whereas PFS and OS with MET FISH-negativity were 15.9 months and 33.0 months, respectively. Univariate analysis revealed that MET FISH-positivity was the most significant independent factor associated with a high risk of progression and death (hazard ratio, 3.83 (p = 0.0008) and 2.25 (p = 0.03), respectively). CONCLUSIONS: Using FISH analysis to detect high polysomy and amplification of MET gene may be useful in predicting shortened PFS and OS after Gefitinib treatment in lung adenocarcinoma. The correlation between MET gene status and clinical outcomes for EGFR-TKI should be further evaluated using large scale samples. FAU - Noro, Rintaro AU - Noro R AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. r-noro@nms.ac.jp. FAU - Seike, Masahiro AU - Seike M AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. mseike@nms.ac.jp. FAU - Zou, Fenfei AU - Zou F AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. zoufenfei@hotmail.com. FAU - Soeno, Chie AU - Soeno C AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. soeno-c@nms.ac.jp. FAU - Matsuda, Kuniko AU - Matsuda K AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. kuniko-m@nms.ac.jp. FAU - Sugano, Teppei AU - Sugano T AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. tetsu629@nms.ac.jp. FAU - Nishijima, Nobuhiko AU - Nishijima N AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. nobu-829@nms.ac.jp. FAU - Matsumoto, Masaru AU - Matsumoto M AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. s7062@nms.ac.jp. FAU - Kitamura, Kazuhiro AU - Kitamura K AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. kazu-k@nms.ac.jp. FAU - Kosaihira, Seiji AU - Kosaihira S AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. say-cos@nms.ac.jp. FAU - Minegishi, Yuji AU - Minegishi Y AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. yminegishi@nms.ac.jp. FAU - Yoshimura, Akinobu AU - Yoshimura A AD - Department of Clinical Oncology, Tokyo Medical University Hospital, Tokyo, Japan. ay1004@tokyo-med.ac.jp. FAU - Kubota, Kaoru AU - Kubota K AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. kkubota@nms.ac.jp. FAU - Gemma, Akihiko AU - Gemma A AD - Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. agemma@nms.ac.jp. LA - eng PT - Journal Article DEP - 20150206 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Quinazolines) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - S65743JHBS (Gefitinib) SB - IM MH - Adenocarcinoma/drug therapy/*genetics/pathology MH - Adenocarcinoma of Lung MH - Adult MH - Aged MH - Disease-Free Survival MH - ErbB Receptors/*genetics MH - Female MH - Gefitinib MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/drug therapy/*genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - *Prognosis MH - Proto-Oncogene Proteins c-met/*biosynthesis/genetics MH - Quinazolines/administration & dosage PMC - PMC4437672 EDAT- 2015/04/18 06:00 MHDA- 2016/01/29 06:00 PMCR- 2015/02/06 CRDT- 2015/04/18 06:00 PHST- 2014/05/13 00:00 [received] PHST- 2015/01/13 00:00 [accepted] PHST- 2015/04/18 06:00 [entrez] PHST- 2015/04/18 06:00 [pubmed] PHST- 2016/01/29 06:00 [medline] PHST- 2015/02/06 00:00 [pmc-release] AID - 10.1186/s12885-015-1019-1 [pii] AID - 1019 [pii] AID - 10.1186/s12885-015-1019-1 [doi] PST - epublish SO - BMC Cancer. 2015 Feb 6;15:31. doi: 10.1186/s12885-015-1019-1.