MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome

Br J Cancer. 2012 Jul 10;107(2):325-33. doi: 10.1038/bjc.2012.237. Epub 2012 May 29.


Background: The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas.

Methods: MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma.

Results: Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis.

Conclusion: MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Chromosomes, Human, Pair 17
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gene Amplification
  • Gene Dosage*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-met / biosynthesis
  • Proto-Oncogene Proteins c-met / genetics*
  • Receptor, ErbB-2 / genetics
  • Retrospective Studies
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism


  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2