title: FGFR4 Is a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Koos
authors.initials: K
authors.lastname: Koole
authors.forename: Pauline M W
authors.initials: PM
authors.lastname: van Kempen
authors.forename: Liselotte W
authors.initials: LW
authors.lastname: van Bockel
authors.forename: Timo
authors.initials: T
authors.lastname: Smets
authors.forename: Zoë
authors.initials: Z
authors.lastname: van der Klooster
authors.forename: Annemiek C
authors.initials: AC
authors.lastname: Dutman
authors.forename: Ton
authors.initials: T
authors.lastname: Peeters
authors.forename: Ron
authors.initials: R
authors.lastname: Koole
authors.forename: Paul
authors.initials: P
authors.lastname: van Diest
authors.forename: Robert J J
authors.initials: RJ
authors.lastname: van Es
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Willems
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000532:radiotherapy; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000532:radiotherapy; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000532:radiotherapy; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4