title: c-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas.
abstract: BACKGROUND
  The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. The aim of this study was to examine the correlations between c-MET/phospho-MET expression as well as MET gene copy number alterations and overall survival (OS) in non-small cell lung carcinomas (NSCLCs).
  
  
  METHODS
  We analyzed 906 NSCLCs including 704 adenocarcinomas (ADCs), 150 squamous cell carcinomas (SCCs), 43 sarcomatoid carcinomas, and 9 large cell carcinomas. The mutational status of epidermal growth factor receptor and K-ras and anaplastic lymphoma kinase rearrangements were retrospectively examined. We performed immunohistochemistry to detect c-MET/phospho-MET expression and MET gene copy number using bright-field in situ hybridization (BISH).
  
  
  RESULTS
  c-MET/phospho-MET expression and MET BISH positivity were observed in 22.2%, 5.6%, and 10.9% of NSCLCs, respectively; they were more prevalent in ADCs (27.3%, 6.9%, and 11.5%, respectively) and sarcomatoid carcinomas (20.9%, 9.3%, and 36.6%, respectively) than in SCCs and large cell carcinomas. Among ADCs, poorly differentiated cases exhibited c-MET expression and MET BISH positivity more commonly than well-differentiated ones. An analysis of all patients revealed that c-MET/phospho-MET expression and MET BISH positivity were not correlated with OS. However, when SCC cases were excluded, both univariate (p=0.019) and multivariate (p=0.020) analyses revealed a significant correlation between MET BISH positivity and OS.
  
  
  CONCLUSIONS
  c-MET/phospho-MET expression and MET BISH positivity differed according to histological type. Among ADCs, c-MET expression and MET BISH positivity were more common in poorly differentiated cases. MET BISH positivity was an independent prognostic factor in nonsquamous NSCLCs.
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan. ktsuta@ncc.go.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kozu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mimae
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; 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