Abstract 921: Fibroblast growth factor receptor 1 (FGFR1) protein expression and gene copy number in small cell lung cancer
Authors: Zhang Liping , Badzio Andrzej , Boyle Theresa , Lu Xian , Dziadziuszko Rafal , Jassem Jacek , Hirsch Fred R. 
Published: May 2015

PURPOSE:

Small cell lung cancer (SCLC) comprises approximately 15% of all lung cancers, corresponding to &gt;30,000 new cases per year in the United States. No major therapeutic progress has been achieved in SCLC in the past 30 years. Identification of new therapies in SCLC is urgently needed. Fibroblast growth factor receptor 1 (FGFR1) is a tyrosine kinase receptor implicated in the pathogenesis of several cancer types and is potentially an attractive target for cancer treatment. FGFR1 amplification and overexpression are known as a frequent event in lung squamous cell carcinoma. However, very little is known about FGFR1 protein expression and gene copy number in SCLC. One difficulty with research on SCLC is the limited availability of tumor specimens sufficient for molecular studies.

METHODS:

We investigated FGFR1 protein expression and gene copy number in a tissue microarray of resected SCLC tumors from 90 patients (67 men and 23 women) from Poland with limited stage. FGFR1 protein expression was assessed by immunohistochemistry (IHC) with H scores ranging from 0 (no expression) to 300 (strong expression in all tumor cells) using a FGFR1 antibody (clone EPR806Y, Origene) . FGFR1 gene copy number was evaluated by dual-color ISH assay using a cocktail of FGFR1 DNP probe (FGFR1 locus on 8p12) and chromosome 8 DIG probe (centromere 8), ultraView SISH DNP detection kit and ultraView Red ISH DIG detection kit (Tucson, AZ, US). Positive FGFR1 protein expression was defined as having an H-score ≥11. FGFR1 gene amplification was defined as FGFR1/CEN8 ratio ≥2.2, or average FGFR1 signals ≥4 per nucleus.

RESULTS:

FGFR1 protein expression was evaluable in 83 of the 90 patients and gene copy number was evaluable in 77 patients. FGFR1 protein expression was positive in 6 cases (7.2%) (mean H score=129, median 70, range: 40-285). FGFR1 gene amplification was observed in 6 cases (7.8 %) of evaluable SCLCs. There were 30%-90% tumor cells containing clusters in the amplified cases. Four of the 6 cases were positive for both FGFR1 protein expression and FGFR1 gene amplification. FGFR1 protein and gene copy number were not associated with patient age, sex, tumor size or overall survival (all p-values &gt;0.15).FGFR1 gene copy number was significantly associated with protein expression (p=0.03, based on a t-test).

CONCLUSIONS: A small subset of patients with SCLC is characterized by tumors with FGFR1 gene amplification and/or FGFR1 protein expression. Further studies are needed to determine whether or not this subset of patients would benefit from FGFR1-directed targeted therapy.

Citation Format: Liping Zhang, Andrzej Badzio, Theresa Boyle, Xian Lu, Rafal Dziadziuszko, Jacek Jassem, Fred R. Hirsch. Fibroblast growth factor receptor 1 (FGFR1) protein expression and gene copy number in small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 921. doi:10.1158/1538-7445.AM2014-921