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Introduction: Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort., Methods: Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation., Results: FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC (p > 0.05)., Conclusion: FGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients.

Objective: 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)., Methods: FGFR4 immunohistochemistry and FGFR4/CEN5q FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. FGFR4 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., Results: The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The FGFR4 gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the FGFR4 Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, FGFR4 gene copy numbers and FGFR4 genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC., Conclusion: 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., (© 2015 S. Karger AG, Basel.)