FGFR1 amplification and FGFR gene fusion in resected squamous cell carcinoma of the lung

Abstract

The objective of the present study was to investigate the clinicopathologic characteristics and prognostic role of FGFR1 amplification and FGFR fusion in patients with surgically resected squamous cell carcinoma of the lung (SCCL). Here, fluorescent in situ hybridization (FISH) was performed to detect FGFR1 amplification and reverse transcriptase polymerase chain reaction (RT-PCR) was used to screen 15 known FGFR fusion variants in 108 patients with surgically resected SCCL. All cases were also analyzed for EGFR, KRAS, HER2 and BRAF mutations. Clinical characteristics including age, sex, smoking status, stage, relapse-free survival (RFS) and overall survival (OS) were collected. Of 108 tumors screened, 14 (13.0%) FGFR1 amplification was found. There were 4 (3.7%) patients that harbored FGFR fusion including 2 BAG4-FGFR1 and 2 FGFR3-TACC3 fusion. Compared to the FGFR1 amplification negative group, patients with FGFR1 amplification were more likely to be smokers (100.0%, 14 of 14 patients, p=0.036), significantly associated with larger tumor (>3 cm) (88.2%, 13 of 14 patients, p=0.032). Patients with FGFR1 amplification had worse RFS (p=0.013) and OS (p=0.021) than those without FGFR1 amplification. There was no correlation between FGFR fusion and clinicopathologic characteristics. No significant difference in RFS or OS was found between patients with FGFR fusion and those without FGFR fusion. In conclusion, FGFR1 amplification and FGFR fusion occurred in 13.0% and 3.7% of patients with surgically resected SCCL, separately. FGFR1 amplification was correlated with poor prognosis and identified a distinct subset of SCCL with a higher prevalence among smokers with relative larger tumor (>3 cm). FGFR is a therapeutic target and patients with FGFR1 amplification or FGFR fusion may benefit from FGFR targeted therapy which needs further clinical investigation.