High MET copy number and MET overexpression: Poor outcome in non-small cell lung cancer patients

Sanghui Park, Yoon La Choi, Chang Ok Sung, Jungsuk An, Jinwon Seo, Myung Ju Ahn, Jin Seok Ahn, Keunchil Park, Young Kee Shin, Ozgur Cem Erkin, Kyung Song, Jhingook Kim, Young Mog Shim, Joungho Han

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

The aim of this study was to evaluate the prevalence and prognostic role of increased gene copy number and protein expression of MET and EGFR in non-small cell lung cancer (NSCLC) patients. Samples were collected from 380 patients with surgically resected NSCLC, and fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) were performed. EGFR amplification and high polysomy (EGFR FISHpositive) were observed in 9.7% and 17.4% of the patients, respectively. EGFR was overexpressed (EGFR IHC-positive) in 19.2% of the patients. Neither EGFR FISH-positive nor EGFR IHC-positive status affected survival after resection. Increased MET copy number (MET FISH-positive by University of Colorado Cancer Center criteria) was observed in 11.1% of the patients (high polysomy, 8.7%; gene amplification, 2.4%). According to the Cappuzzo system, 7.1% of the patients were MET FISH-positive. MET FISH positivity was a negative prognostic factor, especially in patients with adenocarcinoma histology (p=0.040), female gender (p=0.010), old age (p=0.084), and EGFR FISH negativity (p=0.020) at the univariate level but not at the multivariate level. MET was overexpressed (MET IHCpositive) in 13.7% of the patients and associated with shorter overall and disease-free survival (p=0.010 and p=0.056, respectively). Multivariate analysis revealed that MET IHC-positive patients had a significantly increased risk of death (hazard ratio, 1.618; 95% confidence interval, 1.066-2.456; p=0.024). Increased MET copy number and MET overexpression are negative prognostic factors for surgically resected NSCLCs.

Original languageEnglish
Pages (from-to)197-207
Number of pages11
JournalHistology and Histopathology
Volume27
Issue number2
StatePublished - Feb 2012

Keywords

  • EGFR
  • FISH
  • Gene copy number
  • MET
  • Non-small cell lung cancer

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