Clinical significance of MET gene amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum combination chemotherapy.

OBJECTIVE: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting. METHODS: MET amplification was assessed using fluorescence in situ hybridization (FISH) in 50 patients and quantitative polymerase chain reaction (qPCR) in 326 patients; 259 patients treated with first-line fluoropyrimidine and platinum were included for survival analysis. RESULTS: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5 (κ=0.778, P<0.001). Twenty-one out of 326 patients (6.4%) were identified asMET amplification with a copy number of >5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≥2 (33.3% vs. 10.5% P=0.007), peritoneal metastasis (76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels (28.6% vs. 7.3%, P=0.006). The median overall survival (OS) and progression-free survival (PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio (HR)=0.68, 95% confidence interval (95% CI): 0.35-1.32, P=0.254 for PFS; HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS]. CONCLUSIONS: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.