Abstract B31: Fibroblast growth factor receptor-1 (FGFR1) gene amplification is frequent in lung squamous cell carcinoma and high gene copy number indicates a better prognosis in early stage NSCLC.
Authors: Wynes Murry W. , Dziadziuszko Rafal , Wick Nikolaus , Singh Shalini , Ranger-Moore James , Rzyman Witold , Jassem Jacek , Hirsch Fred R. 
Published: June 2012

Introduction: Lung cancer is the leading cause of cancer death globally. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Histologically NSCLC is divided into five subtypes, with adenocarcinoma (AD) and squamous cell carcinoma (SCC) representing the predominant subclasses, 40% and 30%, respectively. Several molecular targets have been identified in AD but such targets in SCC are lacking and there are no FDA-approved targeted agents for SCC. FGFR1 is a druggable receptor tyrosine kinase purported to be an oncogenic driver in lung cancer and the gene has been shown to be amplified in SCC.

Methods: Resection specimens from 32 SCC and 27 non-SCC tumors (22 AD) were evaluated for FGFR1 and chromosome (CH) 8 copy number status using dual-color silver in situ hybridization, black and red, respectively. FGFR1 gene copy number (GCN) and the ratio of FGFR1:CH8 was compared to clinical and pathological characteristics and related to survival.

Results: Of the 59 cases 2 were non-evaluable due to weak staining (one SCC specimen) and lack of sufficient tumor (one non-SCC specimen). The mean and median GCN for FGFR1 were 2.81 (SD±1.17) and 2.36 (range 1.18–6.64) genes/nucleus, respectively, and 1.34 (±0.73) and 1.14 (0.52–5.19) for the FGFR1:CH8 ratio. The average FGFR1 GCN for SCC vs. non-SCC tumors was 3.16 vs 2.38, p=0.02, and the average FGFR1:CH8 ratio was 1.54 vs. 1.10, p=0.03 There were 5 tumors with true FGFR1 amplification, as defined by clusters (all of these SCCs), with an average GCN &gt;4/nucleus. Interestingly, only 3 of these amplified tumors had a FGFR1:CH8 ratio &gt;2. There were 10 tumors, 7 of which were SCC, that contained FGFR1 GCN &gt;3, however only 2 of these had a FGFR1:CH8 ratio &gt;2. There were no associations of FGF1R GCN with age, sex, smoking status, stage or grade. There was a positive association between increased FGFR1 GCN and both DFS and OS (log-rank p= 0.01 and p=0.03, respectively) when using the median (2.36) as the cut-point. However, no associations were seen when evaluating the median (1.14) of the FGFR1:CH8 ratio (log-rank p= 0.93 and p=0.98, respectively).

Conclusions: FGFR1 GCN is highly increased in SCC with 16% of the SSC tumors showing amplification and 48% showing gain (&gt;3). Increased FGFR1 GCN associated with increased DFS and OS but a larger study is warranted to validate this finding. FGFR1 GCN alone appears better at showing gene gain compared to the FGFR1:CH8 ratio. FGFR1 SISH may be a feasible assay to validate whether FGFR1 is a bona fide biomarker for prediction of response and/or outcome to FGFR1 inhibitor therapy in SCC of the lung.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B31.