Analysis of c-Met gene amplification in Japanese patients with advanced non-small cell lung cancer (NSCLC).

Abstract

e18021 Background: Several studies have reported that increased gene copy number (GCN) of c-Met is associated with poor prognosis and resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI). A recent phase II study of mostly Caucasian subjects showed that addition of a c-Met receptor TKI to EGFR-TKI prolonged progression-free survival in NSCLC. It is unclear whether c-Met gene status differs between Caucasians and Asians. Thus, c-Met GCN was evaluated in Japanese patients with advanced NSCLC to determine whether c-Met could be a therapeutic target in Asian patients. EGFR mutation and GCNs of EGFR and Her2 were also analyzed. Methods: Tumor samples suitable for gene amplification and mutation analysis were collected from 40 patients with institutional review board approval. Fluorescence in situ hybridization was used to assess c-Met, EGFR, and Her2 GCNs. DNA was extracted from tumor tissue after micro dissection. PCR and direct sequencing of exons 18, 19, and 21 of the EGFR gene were also performed. Results: Of the 40 patients, 10 (25%) were female, 12 (40.0%) were light or never-smokers, and 34 (85%) had adenocarcinoma. The median age was 63 (range 41-81) years, and 36 patients (90.0%) had a good PS (0-1). The median GCNs of c-Met, EGFR, and Her2 were 1.1 (range 0.3-1.7), 1.1 (range 0.9-7.0), and 1.2 (range 0.9-3.5). No patients had more than 4 c-Met copies. Overall survival was not significantly different between patients with more than 1.1 copies of c-Met and those with less than 1.0 copy of c-Met. GCNs of c-Met, EGFR, and Her2 were not associated with any patients’ characteristics. The c-Met GCN was significantly correlated with Her2 GCN (r=0.401), but not EGFR mutation status or EGFR gene amplification. Thirteen patients were treated with EGFR-TKI; the response rate was higher in patients with EGFR mutations (7/11 vs. 0/2). The mean c-Met GCN was not correlated with EGFR-TKI response (1.08 vs. 1.07). The mean EGFR and Her2 GCNs were higher in EGFR-TKI responders than non-responders (2.91 vs. 1.05, p=0.03; 1.46 vs. 1.12, p=0.053). Conclusions: The c-Met GCN of Japanese NSCLC patients was obviously smaller than in the previous study of Caucasians. There might be ethnic difference in c-Met gene amplification such as EGFR mutation.