Abstract 3662: FGFR2 gene amplification and overexpression frequently occur in squamous cell carcinomas of the lung

Introduction: To date, only a few genetic abnormalities have been reported to be involved in tumorigenesis of squamous cell carcinomas (SqCCs) of the lung. Recently, fibroblast growth factor receptor (FGFR) 1 gene amplification was identified as a potential target for treatment in approximately 20% of SqCCs. In order to identify the clinical significance of FGFR family (FGFR1, FGFR2, FGFR3, and FGFR4) in SqCC, we performed a clinical study on the FGFR family in patients with non-small cell lung cancers (NSCLCs). Methods: Consecutive 138 NSCLC patients were studied. Gene expressions of FGFR family were evaluated by quantitative real-time RT-PCR. Intratumoral protein expressions of FGFR1, FGFR2, and Ki-67 were evaluated by immunohistochemistry. Gene amplifications of FGFR1 and FGFR2 were investigated by FISH. In addition, mutations of EGFR (exon 19-22) and KRAS (exon 1) were also investigated using either PCR-SSCP or PCR-RFLP, confirmed by direct sequencing. Results: Among 138 NSCLCs, 91 tumors were adenocarcinoma, 37 tumors were SqCCs, and 10 tumors were other types. Regarding FGFR gene expressions in NSCLCs, The FGFR2 gene expression was significantly higher in NSCLCs with both wild-type EGFR and wild-type KRAS than in NSCLCs with either mutant EGFR or mutant KRAS (P = 0.0012). FGFR2 gene expression was significantly higher in SqCCs than in adenocarcinomas (P < 0.0001). Furthermore, the FGFR2 gene expression was the highest among the gene expressions of FGFR family in SqCC. In contrast, no significant difference was observed in FGFR1 gene expression in relation to tumor histology. Regarding FGFR protein expressions in NSCLCs, the intratumoral FGFR2 protein expression significantly correlated with the FGFR2 gene expression (P < 0.0001, r = 0.5492), and the intratumoral FGFR2 protein expression was also significantly higher in SqCCs than in adenocarcinomas (P = 0.0008). Furthermore, the FGFR2 protein expression significantly correlated with Ki-67 proliferation index (P < 0.0001, r = 0.4677). In FISH analysis, FGFR1 gene amplification was detected in 34.3% (12/35) of SqCCs, and FGFR2 gene amplification was detected in 22.9% (8/35) of SqCCs. Furthermore, the Ki-67 proliferation index was significantly higher in SqCCs with FGFR2 gene amplification than in SqCCs without FGFR2 gene amplification (P = 0.0069). Conclusions: FGFR2 gene amplification and overexpression frequently occur and correlate with the tumor proliferation in SqCCs of the lung. FGFR2 could be a