MET FISH-positive status predicts short progression-free survival and overall survival after gefitinib treatment in lung adenocarcinoma with EGFR mutation

BMC Cancer

Research Article

Akinobu Yoshimura¹  Rintaro Noro²  Masahiro Seike²  Kuniko Matsuda²  Kazuhiro Kitamura²  Yuji Minegishi²  Teppei Sugano²  Nobuhiko Nishijima²  Kaoru Kubota²  Akihiko Gemma²  Seiji Kosaihira²  Fenfei Zou²  Chie Soeno²  Masaru Matsumoto² 

[1] Department of Clinical Oncology, Tokyo Medical University Hospital, Tokyo, Japan;Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan;

关键词: MET;    Lung cancer;    in situ;    Gefitinib;    EGFR mutation;   

DOI  :  10.1186/s12885-015-1019-1

 received in 2014-05-13, accepted in 2015-01-13,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundLung 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.MethodsWe 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).ResultsFISH 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).ConclusionsUsing 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.

【 授权许可】

Unknown   
© Noro et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.