Increased MET Gene Copy Number Negatively Affects Survival of Surgically Resected Non–Small-Cell Lung Cancer Patients
| Autor: | Maria Grazia Sciarrotta, Lara Felicioni, Annarita Destro, Massimo Roncalli, M. Varella-Garcia, Matteo Incarbone, Giovanna Finocchiaro, Maela Del Grammastro, F Buttitta, Margaret Skokan, Sujatha Gajapathy, Elisa Rossi, Marco Alloisio, Federico Cappuzzo, Luigi Terracciano, Antonio Marchetti, Armando Santoro, Luca Toschi |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Lung Neoplasms DNA Mutational Analysis Gene Dosage Kaplan-Meier Estimate Gene dosage Carcinoma Non-Small-Cell Lung Proto-Oncogene Proteins Original Reports medicine Carcinoma Biomarkers Tumor Humans Receptors Growth Factor Copy-number variation Epidermal growth factor receptor Lung cancer In Situ Hybridization Fluorescence Aged Retrospective Studies Aged 80 and over biology business.industry Respiratory disease Cancer Middle Aged Proto-Oncogene Proteins c-met medicine.disease Prognosis MET Exon 14 Skipping Mutation ErbB Receptors Oncology Tissue Array Analysis Cancer research biology.protein Female business |
| Popis: | 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+. 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. |
| Databáze: | OpenAIRE |
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