Correlation between MET gene copy number by silver in situ hybridization and protein expression by immunohistochemistry in non-small cell lung cancer

J Thorac Oncol. 2012 Feb;7(2):340-7. doi: 10.1097/JTO.0b013e318240ca0d.


Purpose: The MET receptor is involved in the pathogenesis and progression of non-small cell lung cancer (NSCLC). Clinical trials with MET inhibitors in NSCLC are planned with patient selection based on immunohistochemistry (IHC) and/or gene copy number assessment. Therefore, a detailed understanding of relationship between these markers and prognosis is essential.

Methods: This study included tumors from 189 patients with NSCLC who underwent pulmonary resection (median follow-up, 5.3 years). MET expression was evaluated by IHC on tissue microarrays and scored according to hybrid (H) score (range: 0-400) and by scoring system used in the MetMAb trial (≥ 50% of cells with moderate or strong staining). MET gene copy number was assessed by silver in situ hybridization (n =140 patients).

Results: Median MET IHC H score was 60 (range: 0-400; n =174). There were no associations between clinical and pathological characteristics, disease-free survival, and overall survival according to median value (p =0.36 and p =0.38, respectively), or other cut-points. According to MetMAb scoring criteria, IHC positivity rate was 25%, again with no associations to clinicopathological features or survival. In 140 tumors evaluable for MET copy number, 3 (2.1%) showed gene amplification and 14 (10%) had tumors with average of 5 or more copies per nucleus. There were no associations of MET copy number with clinical characteristics, disease-free survival, or overall survival with any analyzed cut-points. Correlation between MET copy number and protein expression was significant (Pearson's r =0.42, p < 0.0001).

Conclusions: There is a significant correlation between MET protein expression and MET gene copy number in operable NSCLC, but neither is associated with prognosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gene Amplification
  • Gene Dosage*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism*
  • Survival Rate
  • Tissue Array Analysis


  • MET protein, human
  • Proto-Oncogene Proteins c-met