Fibroblast Growth Factor Receptor 1 Gene Amplification Is Associated With Poor Survival and Cigarette Smoking Dosage in Patients With Resected Squamous Cell Lung Cancer

Abstract

PURPOSE: To investigate the frequency and the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected squamous cell carcinoma of the lung (SCCL) and the association between smoking and FGFR1 amplification. PATIENTS AND METHODS: Gene copy number of FGFR1 was investigated in microarrayed tumors from 262 patients with SCCL who had tumor tissue as well as smoking and survival data available. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1-amplified tumor (FGFR1 amp(+)) was prespecified as a tumor with nine or more copies of FGFR1. RESULTS: Among 262 patients, the frequency of FGFR1 amp(+) was 13.0%. Patients with FGFR1 amp(+) had significantly shorter disease-free survival (DFS; 26.9 v 94.6 months; P < .001) as well as shorter overall survival (OS; 51.2 v 115.0 months; P = .002) than those without FGFR1 amp(+). Multivariate modeling confirmed that patients with FGFR1 amp(+) had a significantly greater risk of recurrence and death than those without FGFR1 amp(+) after adjusting for sex, smoking status, pathologic stage, and adjuvant chemotherapy (DFS: adjusted hazard ratio [AHR], 2.24; 95% CI, 1.45 to 3.45; P < .001; OS: AHR, 1.83; 95% CI, 1.15 to 2.89; P = .01). The frequency of FGFR1 amp(+) was significantly higher in current smokers than in former smokers and never-smokers (28.9% v 2.5% v 0%; P(trend) < .001). As the smoking dosage increased, so did the incidence of FGFR1 amp(+) (P(trend) = .002). CONCLUSION: FGFR1 amplification is an independent negative prognostic factor in surgically resected SCCL and is associated with cigarette smoking in a dose-dependent manner. FGFR1 amplification is a relevant therapeutic target in Asian patients with SCCL.