Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients

Federico Cappuzzo, Antonio Marchetti, Margaret Skokan, Elisa Rossi, Sujatha Gajapathy, Lara Felicioni, Maela Del Grammastro, Maria Grazia Sciarrotta, Fiamma Buttitta, Matteo Incarbone, Luca Toschi, Giovanna Finocchiaro, Annarita Destro, Luigi Terracciano, Massimo Roncalli, Marco Alloisio, Armando Santoro, Marileila Varella-Garcia

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Purpose 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). Patients and 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 ≥ 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+.Inthe 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). Conclusion MET increased gene copy number is an independent negative prognostic factor in surgically resected NSCLC. EGFR gene gain does not impact survival after resection.

Original languageEnglish
Pages (from-to)1667-1674
Number of pages8
JournalJournal of Clinical Oncology
Issue number10
Publication statusPublished - Apr 1 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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