Abstract
ObjectiveTo investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting. MethodsMET 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. ResultsThe 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]. ConclusionsqPCR 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.
Highlights
Despite improvements in outcomes with targeted agents, including trastuzumab [1], ramucirumab [2] and apatinib [3], the prognosis of unresectable or metastatic gastric cancer remains unfavourable
We found that MET gene amplification was not associated with the prognosis of patients with metastatic or locally advanced unresectable gastric cancers who were treated with palliative fluoropyrimidine and platinum (FP) chemotherapy
Matsusaka et al reported that MET gene amplification was associated with overall survival (OS), but not with progression-free survival (PFS) in 150 patients who were uniformly treated with S-1 and cisplatin for metastatic or recurrent gastric cancer, which needs careful interpretation since patients received the same regimen and the MET amplification was assessed by real-time PCR [29]
Summary
Despite improvements in outcomes with targeted agents, including trastuzumab [1], ramucirumab [2] and apatinib [3], the prognosis of unresectable or metastatic gastric cancer remains unfavourable. Little is known about the clinicopathologic features and prognosis of MET-amplified gastric cancer, studies suggested worse survival outcomes for METamplified gastric cancer patients based on resected tissue obtained during curative surgery [11,17,18,20]. Based on these findings, there are some limitations for patients with metastatic or unresectable gastric cancer who are indicated for palliative chemotherapy. We investigated the efficacy of qPCR to screen MET gene amplification and determined the clinicopathologic features and prognosis of MET gene copy number gain in patients with locally advanced unresectable or metastatic gastric cancer
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