mRNA Expression of FGFR1 as Potential Marker for Predicting Prognosis of Surgical Resection of Small Cell Lung Cancer may be better than Protein Expression and Gene Amplification

Purpose: Fibroblast growth factor receptor 1 (FGFR1) alterations have been described in many cancers, including lung cancer, but the role has not been elucidated specifically in small cell lung cancer (SCLC). The present study aimed to identify the frequency of FGFR1 alterations among Chinese patients with surgically resected SCLC and the association with the clinicopathological characteristics and the survival were also investigated. Methods: FGFR1 protein expression, FGFR1 amplification, FGFR1 mutations, and messenger RNA (mRNA) levels, were determined by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR), respectively in primary tumors from 33 patients with resected SCLC. Results: 7/33(21.2%) of the specimens were positive for FGFR1 protein expression. FGFR1 amplification was identified in 4/28 cases (14.3%). If the cut-off value was determined to be 3.5, FGFR1 mRNA positivity was considered in 7/33 cases (21.2%). However, no mutation was detected in the 33 SCLC postoperative tissue specimens. No significant association was observed between FGFR1 protein expression or amplification and clinicalcharacteristics or prognosis. There was a distinct trend for mRNA level and poor prognosis, including recurrence-free survival (RFS) (p = 0.07) and overall survival (OS) (p= 0.08), but they did not reach statistical significance. Conclusions: As novel FGFR1-targeted therapies are developed, FISH, IHC, especially mRNA were detected, which should be considered as biomarkers of FGFR1 pathway dysregulation in SCLC.