High MET copy number and MET overexpression: Poor outcome in non-small cell lung cancer patients
Sanghui Park1, Yoon-La Choi2, Chang Ok Sung2, Jungsuk An1, Jinwon Seo3, Myung-Ju Ahn4, Jin Seok Ahn4, Keunchil Park4, Young Kee Shin5, Ozgur Cem Erkin5, Kyung Song5, Jhingook Kim6, Young Mog Shim6 and Joungho Han2
1Department of Pathology, Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea, 2Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 3Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea, 4Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 5Research Institute of Pharmaceutical Science, Department of Pharmacy, Seoul National University College of Pharmacy, Seoul, Korea and 6Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Offprint requests to: Jungho Han, M.D., Ph.D. or Yoon-La Choi, M.D., Ph.D., Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. e-mail: firstname.lastname@example.org /email@example.com
Summary. 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 FISH-positive) 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 IHC-positive) 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. Histol Histopathol 27, 197-207 (2012)
Key words: MET, EGFR, Non-small cell lung cancer, FISH, Gene copy number