title: Amplification and overexpression of CMET is a common event in brain metastases of non-small cell lung cancer.
abstract: BACKGROUND
  CMET represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We investigated CMET gene amplification status by fluorescence in-situ hybridization (FISH) and CMET protein expression by immunohistochemistry in a large series of 209 NSCLC brain metastases (BM; 165 adenocarcinoma, 20 squamous cell carcinoma, 11 adenosquamous carcinomas, 11 large cell carcinomas and two large cell neuroendocrine carcinomas) and correlated our results to clinic-pathological parameters and molecular data from previous studies.
  
  
  RESULTS
  We found CMET gene amplification in 36/167 (21.6%) and CMET protein expression in 87/196 (44.4%) of evaluable BM. There was a strong correlation between the presence of CMET gene amplification and CMET protein expression (P < 0.001, chi-square test). Furthermore, presence of CMET amplification correlated positively with presence of ALK amplifications (P = 0.039, chi-square test) and high HIF1 alpha index (P = 0.013, Mann-Whitney U-test). Neither CMET expression nor CMET gene amplification status correlated with patient outcome parameters or known prognostic factors.
  
  
  CONCLUSIONS
  CMET overexpression and CMET amplification are commonly found in NSCLC BM and may represent a promising therapeutic target.
authors.affiliation: Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Georg
authors.initials: G
authors.lastname: Widhalm
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckmann
authors.forename: Adelheid
authors.initials: A
authors.lastname: Wöhrer
authors.forename: Monika
authors.initials: M
authors.lastname: Hackl
authors.forename: Christoph
authors.initials: C
authors.lastname: Zielinski
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary*; D018196:Carcinoma, Adenosquamous / Q000473:pathology*; D018287:Carcinoma, Large Cell / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism
chemical_list: D019859:Proto-Oncogene Proteins c-met
keywords: CMET; brain metastases; fluorescence in-situ hybridization; immunohistochemistry; lung cancer; prognosis