title: Correlation between MET gene copy number by silver in situ hybridization and protein expression by immunohistochemistry in non-small cell lung cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Medical University of Gdansk, Gdansk, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Dziadziuszko
authors.forename: Murry W
authors.initials: MW
authors.lastname: Wynes
authors.forename: Shalini
authors.initials: S
authors.lastname: Singh
authors.forename: Bernadette Reyna
authors.initials: BR
authors.lastname: Asuncion
authors.forename: James
authors.initials: J
authors.lastname: Ranger-Moore
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Konopa
authors.forename: Witold
authors.initials: W
authors.lastname: Rzyman
authors.forename: Barbara
authors.initials: B
authors.lastname: Szostakiewicz
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met