title: MET immunolabelling is a useful predictive tool for MET gene amplification in glioblastoma.
abstract: OBJECTIVE
  MET gene amplification is rare in glioblastoma (GBM) and represents a potential target for MET inhibitors. An immunohistochemical screening may be useful to identify MET amplification. The aim of our study was to establish how MET immunolabelling correlates with MET amplification.
  
  
  METHODS
  Three cohorts including 108 GBM (cohort 1, prospective), 104 GBM (cohort 2, retrospective) and 52 GBM (cohort 3, prospective) were investigated for MET expression by immunohistochemistry. MET amplification was assessed by comparative genomic hybridization on microarray (CGH-array) in all cohorts and by fluorescent in situ hybridization (FISH) in cohorts 2 and 3. Active form of MET was assessed using p-MET (Y1349) immunohistochemistry.
  
  
  RESULTS
  Diffuse MET amplification detectable by CGH-array was associated with diffuse, strong MET immunolabelling (four cases in cohort 1 and one case in cohort 2). Focal MET amplification detectable only by FISH was observed in small foci of strongly immunopositive cells in two GBM (cohort 2). In both cohorts, MET amplification was never detected in GBM devoid of strongly immunopositive cells. MET overexpression, observed in 23% of unamplified GBM, was associated with a predominant weak-to-moderate staining intensity and with necrosis (P < 0.005). p-MET was detected in all MET-amplified GBM and in perinecrotic areas of nonamplified GBM. A strong MET immunostaining intensity, at least focal and distant from necrosis, showed 100% sensitivity and 84% specificity for predicting MET amplification in cohort 3.
  
  
  CONCLUSIONS
  MET amplification is characterized by strongly immunopositive cells. Only GBM showing strong MET immunostaining is appropriate for the assessment of MET amplification.
authors.affiliation: Department of Pathology, University Hospital of Nice, Nice, France.|UMR CNRS 7277-UMR INSERM 1091, Institute of Biology Valrose, University of Nice, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: Burel-Vandenbos
authors.affiliation: Department of Pathology, University Hospital of Nice, Nice, France.
authors.forename: M
authors.initials: M
authors.lastname: Ngo-Mai
authors.affiliation: Department of Pathology, University Hospital of Nice, Nice, France.
authors.forename: B
authors.initials: B
authors.lastname: Dadone
authors.affiliation: Laboratory of Solid Tumors Genetics, University Hospital of Nice, Nice, France.|Institute for Research on Cancer and Aging, Nice, France.
authors.forename: I
authors.initials: I
authors.lastname: Di Mauro
authors.affiliation: Laboratory of Solid Tumors Genetics, University Hospital of Nice, Nice, France.|Institute for Research on Cancer and Aging, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Gimet
authors.affiliation: Department of Oncology, Centre Antoine Lacassagne, Nice, France.
authors.forename: E
authors.initials: E
authors.lastname: Saada-Bouzid
authors.affiliation: Department of Neurology, University Hospital of Nice, Nice, France.
authors.forename: V
authors.initials: V
authors.lastname: Bourg
authors.affiliation: UMR CNRS 7277-UMR INSERM 1091, Institute of Biology Valrose, University of Nice, Nice, France.|Department of Neurosurgery, University Hospital of Nice, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: Almairac
authors.affiliation: Department of Neurosurgery, University Hospital of Nice, Nice, France.
authors.forename: D
authors.initials: D
authors.lastname: Fontaine
authors.affiliation: UMR CNRS 7277-UMR INSERM 1091, Institute of Biology Valrose, University of Nice, Nice, France.
authors.forename: T
authors.initials: T
authors.lastname: Virolle
authors.affiliation: Laboratory of Solid Tumors Genetics, University Hospital of Nice, Nice, France.|Institute for Research on Cancer and Aging, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: 
  MET
  ; gene amplification; glioblastoma; immunohistochemistry