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

doi:10.1159/000439536

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

School of Medicine

Research output: Contribution to journal › Article

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 language	English (US)
Pages (from-to)	280-289
Number of pages	10
Journal	Pathobiology
Volume	82
Issue number	6
DOIs	https://doi.org/10.1159/000439536
State	Published - Nov 1 2015

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

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Koole, K., Van Kempen, P. M. W., Van Bockel, L. W., Smets, T., Van Der Klooster, Z., Dutman, A. C., Peeters, T., Koole, R., Van Diest, P., Van Es, R. J. J., & 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 journal › Article

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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.",

keywords = "Biomarker, Fibroblast growth factor receptor 4, Oral cancer, Oropharyngeal cancer, Therapeutic target",

author = "Koos Koole and {Van Kempen}, {Pauline M.W.} and {Van Bockel}, {Liselotte W.} and Timo Smets and {Van Der Klooster}, Zo{\"e} and Dutman, {Annemiek C.} and Ton Peeters and Ron Koole and {Van Diest}, Paul and {Van Es}, {Robert J.J.} and Willems, {Stefan M.}",

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T1 - FGFR4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma

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.

KW - Biomarker

KW - Fibroblast growth factor receptor 4

KW - Oral cancer

KW - Oropharyngeal cancer

KW - Therapeutic target

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