MET Amplification (MET/CEP7 Ratio ≥ 1.8) Is an Independent Poor Prognostic Marker in Patients With Treatment-naive Non–Small-cell Lung Cancer

The MET pathway is a promising target in patients with non–small-cell lung cancer (NSCLC). Fluorescence in situ hybridization analysis has become a standard method to detect MET amplification. However, no consensus has been reached regarding the definition of MET amplification. We aimed to find clinically meaningful cutoffs for MET amplification that could be used as a prognostic marker and/or indication for MET inhibitor therapy. We reviewed the fluorescence in situ hybridization results of MET/CEP7 (centromere of chromosome 7) for 2260 patients with treatment-naive NSCLC from 2014 to 2019. Clinical and pathologic data were collected from the medical records. Log-rank tests and Cox proportional hazard models were used to estimate the overall survival (OS) among patients with different MET/CEP7 ratios and/or MET copy numbers. Of the 2260 patients, 130 (5.8%) had had a MET/CEP7 ratio of ≥ 1.8 and 13 (0.6%) had had a ratio of ≥ 5.0. Of these 130 patients with a MET/CEP7 ratio of ≥ 1.8, 123 (95%) also had a MET copy number of ≥ 5. In general, a higher MET copy number and higher MET/CEP7 ratio were associated with advanced tumor stage. The OS was significantly shorter when the MET copy number was ≥ 10 and/or when the MET/CEP7 ratio was ≥ 1.8. A MET/CEP7 ratio of ≥ 1.8 remained a significant hazard to OS on multivariate analysis (hazard ratio, 1.63; P = .019). Patients with a MET copy number of ≥ 10 and/or MET/CEP7 ratio of ≥ 1.8 showed significantly poorer survival, and a MET/CEP7 ratio of ≥ 1.8 was an independent poor prognostic factor. •Approximately 5.8% of NSCLC cases will have a MET/CEP7 ratio of ≥ 1.8, and ~0.6% of NSCLC cases will have a MET/CEP7 ratio of ≥ 5.•A MET/CEP7 ratio of ≥ 1.8 is an independent poor prognostic marker in NSCLC.•Patients with a MET/CEP7 ratio of ≥ 5 are the most likely to benefit from MET inhibitor therapy. The association of MET amplification with survival has remained controversial. We studied 2260 patients with treatment-naive non–small-cell lung cancer who had undergone fluorescence in situ hybridization for MET/CEP7 (centromere of chromosome 7). Of the patients, 5.8% had a MET/CEP7 ratio of ≥ 1.8 and 2.8% a MET copy number of ≥ 10. A MET/CEP7 ratio of ≥ 1.8 and/or MET copy number of ≥ 10 were associated with inferior outcomes, and a MET/CEP7 ratio of ≥ 1.8 was an independent poor prognostic marker.