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 as MET 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.