Associations of C-MET Gene Copy with EGFR Mutation and Gene Copy in EGFR-Tyrosine Kinase Inhibitor (TKI) Untreated Non-Small Cell Lung Cancer (NSCLC)
JM Bae, YK Jeon, YT Kim, JW Seo, YA Kim, DH Chung. Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea; Seoul City Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
Background: C-Met is transmembrane receptor tyrosine kinase for HGF/SF, and known to be frequently amplified in NSCLC patients with secondary EGFR-TKI resistance. However, C-MET gene amplification rates have been variably reported, and the association of C-MET amplification with EGFR gene mutation and gene copy is not well known in EGFR-TKI untreated NSCLC patients. Here we investigated the clinicopathologic characteristics of C-MET amplification, EGFR mutation and gene copy number in EGFR-TKI untreated NSCLC.
Design: All 216 NSCLC patients (124 adenocarcinomas, 62 squamous cell carcinomas, and 30 others) were Korean, and FFPE tissues were obtained from surgically resected specimen. EGFR mutations (exon 18, 19, 20, 21) were analyzed using PCR based direct sequencing. EGFR and C-MET gene copy numbers were analyzed using fluorescence in situ hybridization (FISH) and estimated according to the University of Colorado Cancer Center (UCCC) criteria for EGFR and Cappuzzo scoring system for C-MET.
Results: EGFR mutations were observed in 32.4% (n = 70) and increased EGFR gene numbers (EGFR FISH-positive) were found in 31.5% (n = 68). EGFR mutation and increased gene copy were strongly associated with female (p < 0.001 and 0.002), non-smoker (p < 0.001 and 0.001), and adenocarcinoma histology (p < 0.001, and 0.02). Increased EGFR gene copy was associated with advanced stage (p = 0.032) and distant metastasis (p = 0.002). Increased C-MET gene copy (mean ≥ 5 per cell) was observed in 6.5% (n = 14, which included 6 adenocarcinomas, 4 squamous cell carcinomas and 4 others), and true amplification was observed in 2.3% (n = 5). Increased C-MET gene copy showed weak association with EGFR FISH-positive (p = 0.041) and advanced stage (p = 0.047), but was not associated with EGFR mutation, age, gender, smoking history and histology. Four patients (3 adenocarcinoma and 1 pleomorphic carcinoma) had both increased C-MET gene copy and EGFR mutation and were EGFR FISH-positive.
Conclusions: Increased C-MET gene copy was weakly associated with EGFR FISH positive and advanced stage in NSCLC. A small set of EGFR-TKI untreated NSCLC patients had both C-MET amplification and EGFR mutation.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 254, Tuesday Morning