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BACKGROUND   MET  gene amplification and Met protein overexpression may be associated with a poor prognosis. The  MET /Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry–based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of  MET /Met in gastroesophageal adenocarcinoma (GEC).    METHODS  Samples from 447 GEC patients were analyzed for  MET  gene amplification (FISH) and Met protein expression (IHC and SRM). Cox proportional hazards models and Kaplan‐Meier estimates were applied to explore relations between Met, overall survival (OS), and clinical/pathological characteristics. Spearman's rank coefficient was used to assess the correlation between parameters.    RESULTS  Patients with  MET ‐amplified tumors had worse OS when: the  MET /centromere enumeration probe for chromosome 7 FISH ratio was ≥ 2 (hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.84‐5.33), the  MET  gene copy number was ≥5 (HR, 2.51; 95% CI, 1.45‐4.34), or ≥ 10% of the cells had ≥15 copies (HR, 4.28; 95% CI, 2.18‐8.39). Similar observations were made with Met protein overexpression by IHC (≥1 + intensity in ≥ 25% of the tumor cell membrane: HR, 1.39; 95% CI, 1.04‐1.86) or SRM (≥400 amol/μg: HR, 1.76; 95% CI, 1.06‐2.90). A significant correlation was observed between  MET  FISH/Met IHC,  MET  FISH/Met SRM, and Met IHC/Met SRM; only  MET  FISH and Met SRM were independent negative prognostic biomarkers in multivariate analyses.    CONCLUSIONS   MET  amplification and overexpression, assessed by multiple methods, were associated with a worse prognosis in univariate analyses. However, only  MET  amplification by FISH and Met expression by SRM were independent prognostic biomarkers. Compared with IHC, SRM may provide an added benefit for informed decisions about Met‐targeted therapy.   Cancer  2017;123:1061–70.  ©  2016 American Cancer Society .

MET tyrosine kinase receptor expression and amplification as prognostic biomarkers of survival in gastroesophageal adenocarcinoma