title: Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients.
abstract: OBJECTIVE
  To investigate the prognostic role of genomic gain for MET and epidermal growth factor receptor (EGFR) genes in surgically resected non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  This retrospective study included 447 NSCLC patients with available tumor tissue from primary lung tumor and survival data. EGFR and MET status was evaluated by fluorescent in situ hybridization (FISH) in tissue microarray sections.
  
  
  RESULTS
  EGFR FISH results were obtained in 376 cases. EGFR gene amplification and high polysomy (EGFR FISH+) were observed in 10.4% and 32.4% of cases, respectively. EGFR FISH-positive patients had a nonsignificant shorter survival than EGFR FISH-negative patients (P = .4). Activating EGFR mutations were detected in 9.7% of 144 stage I-II disease with no impact on survival. MET FISH analysis was performed in 435 cases. High MET gene copy number (mean > or = 5 copies/cell) was observed in 48 cases (MET+, 11.1%), including 18 cases with true gene amplification (4.1%). MET+ status was associated with advanced stage (P = .01), with grade 3 (P = .016) and with EGFR FISH+ result (P < .0001). No patient with activating EGFR mutation resulted MET+. In the whole population, MET-positive patients had shorter survival than MET-negative patients (P = .005). Multivariable model confirmed that MET-negative patients had a significant reduction in the risk of death than MET-positive patients (hazard ratio, 0.66; P = .04).
  
  
  CONCLUSIONS
  MET increased gene copy number is an independent negative prognostic factor in surgically resected NSCLC. EGFR gene gain does not impact survival after resection.
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico, Department of Oncology-Hematology, University of Milan School of Medicine, IRCCS Istituto Clinico Humanitas, Rozzano, Italy. federico.cappuzzo@humanitas.it
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchetti
authors.forename: Margaret
authors.initials: M
authors.lastname: Skokan
authors.forename: Elisa
authors.initials: E
authors.lastname: Rossi
authors.forename: Sujatha
authors.initials: S
authors.lastname: Gajapathy
authors.forename: Lara
authors.initials: L
authors.lastname: Felicioni
authors.forename: Maela
authors.initials: M
authors.lastname: Del Grammastro
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sciarrotta
authors.forename: Fiamma
authors.initials: F
authors.lastname: Buttitta
authors.forename: Matteo
authors.initials: M
authors.lastname: Incarbone
authors.forename: Luca
authors.initials: L
authors.lastname: Toschi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Finocchiaro
authors.forename: Annarita
authors.initials: A
authors.lastname: Destro
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.forename: Marco
authors.initials: M
authors.lastname: Alloisio
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000235:genetics*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met