FGFR4 Is a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma

Abstract

<b><i>Objective:</i></b> The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). <b><i>Methods:</i></b> FGFR4 immunohistochemistry and <i>FGFR4</i>/<i>CEN5q</i> FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. <i>FGFR4</i> genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy. <b><i>Results:</i></b> The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The <i>FGFR4 </i>gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the <i>FGFR4</i> Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, <i>FGFR4 </i>gene copy numbers and <i>FGFR4 </i>genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC. <b><i>Conclusion:</i></b> FGFR4 is frequently overexpressed in OSCC and OPSCC in the absence of gene amplification, and may serve as a potential predictive marker for FGFR4-directed targeted therapy in OSCC and OPSCC.