FGFR4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma

Koos Koole, Pauline M W Van Kempen, Liselotte W. Van Bockel, Timo Smets, Zoë Van Der Klooster, Annemiek C. Dutman, Ton Peeters, Ron Koole, Paul Van Diest, Robert J J Van Es, Stefan M. Willems

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)280-289
Number of pages10
JournalPathobiology
Volume82
Issue number6
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

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Receptor, Fibroblast Growth Factor, Type 4
Squamous Cell Carcinoma
Biomarkers
Radiotherapy
Genotype
Gene Dosage
Survival
Gene Amplification
Ambulatory Care

Keywords

  • Biomarker
  • Fibroblast growth factor receptor 4
  • Oral cancer
  • Oropharyngeal cancer
  • Therapeutic target

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Koole, K., Van Kempen, P. M. W., Van Bockel, L. W., Smets, T., Van Der Klooster, Z., Dutman, A. C., ... Willems, S. M. (2015). FGFR4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma. Pathobiology, 82(6), 280-289. https://doi.org/10.1159/000439536

FGFR4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma. / Koole, Koos; Van Kempen, Pauline M W; Van Bockel, Liselotte W.; Smets, Timo; Van Der Klooster, Zoë; Dutman, Annemiek C.; Peeters, Ton; Koole, Ron; Van Diest, Paul; Van Es, Robert J J; Willems, Stefan M.

In: Pathobiology, Vol. 82, No. 6, 01.11.2015, p. 280-289.

Research output: Contribution to journalArticle

Koole, K, Van Kempen, PMW, Van Bockel, LW, Smets, T, Van Der Klooster, Z, Dutman, AC, Peeters, T, Koole, R, Van Diest, P, Van Es, RJJ & Willems, SM 2015, 'FGFR4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma', Pathobiology, vol. 82, no. 6, pp. 280-289. https://doi.org/10.1159/000439536
Koole K, Van Kempen PMW, Van Bockel LW, Smets T, Van Der Klooster Z, Dutman AC et al. FGFR4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma. Pathobiology. 2015 Nov 1;82(6):280-289. https://doi.org/10.1159/000439536
Koole, Koos ; Van Kempen, Pauline M W ; Van Bockel, Liselotte W. ; Smets, Timo ; Van Der Klooster, Zoë ; Dutman, Annemiek C. ; Peeters, Ton ; Koole, Ron ; Van Diest, Paul ; Van Es, Robert J J ; Willems, Stefan M. / FGFR4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma. In: Pathobiology. 2015 ; Vol. 82, No. 6. pp. 280-289.
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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. 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.",
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AU - Koole, Koos

AU - Van Kempen, Pauline M W

AU - Van Bockel, Liselotte W.

AU - Smets, Timo

AU - Van Der Klooster, Zoë

AU - Dutman, Annemiek C.

AU - Peeters, Ton

AU - Koole, Ron

AU - Van Diest, Paul

AU - Van Es, Robert J J

AU - Willems, Stefan M.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

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KW - Oropharyngeal cancer

KW - Therapeutic target

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