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

Cappuzzo, Federico and Marchetti, Antonio and Skokan, Margaret and Rossi, Elisa and Gajapathy, Sujatha and Felicioni, Lara and Del Grammastro, Maela and Sciarrotta, Maria Grazia and Buttitta, Fiamma and Incarbone, Matteo and Toschi, Luca and Finocchiaro, Giovanna and Destro, Annarita and Terracciano, Luigi and Roncalli, Massimo and Alloisio, Marco and Santoro, Armando and Varella-Garcia, Marileila. (2009) Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 27. pp. 1667-1674.

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Official URL: http://edoc.unibas.ch/dok/A6003042

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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 < 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). 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.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
UniBasel Contributors:Terracciano, Luigi M.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Clinical Oncology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:13

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