Abstract
Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor tyrosine kinase family. It has been identified as a promising therapeutic target in multiple types of cancer. We have investigated FGFR3 protein expression and FGFR3 gene copy-numbers in a single well-documented cohort of oral and oropharyngeal squamous cell carcinoma. Tissue microarray sets containing 452 formalin-fixed paraffin-embedded tissues were immunohistochemically stained with an anti-FGFR3 antibody and hybridized with a FGFR3 fluorescence in situ hybridization probe. FGFR3 protein expression was correlated with clinicopathological and survival data, which were retrieved from electronic medical records. FGFR3 mRNA data of 522 head and neck squamous cell carcinoma (HNSCC) were retrieved from The Cancer Genome Atlas (TCGA). Fibroblast growth factor receptor 3 (FGFR3) protein was overexpressed in 48% (89/185) of oral and 59% (124/211) of oropharyngeal squamous cell carcinoma. Overexpression of FGFR3 protein was not related to overall survival or disease-free survival in oral (HR[hazard ratio]: 0.94; 95% CI: 0.64-1.39; P=0.77, HR: 0.94; 95% CI: 0.65-1.36; P=0.75) and oropharyngeal squamous cell carcinoma (HR: 1.21; 95% CI: 0.81-1.80; P=0.36, HR: 0.42; 95% CI: 0.79-1.77; P=0.42). FGFR3 mRNA was upregulated in 3% (18/522) of HNSCC from the TCGA. The FGFR3 gene was gained in 0.6% (1/179) of oral squamous cell carcinoma but no amplification was found in oral and oropharyngeal squamous cell carcinoma. In conclusion, FGFR3 protein is frequently overexpressed in oral and oropharyngeal squamous cell carcinoma. Therefore, it may serve as a potential therapeutic target for FGFR3-directed therapies in oral and oropharyngeal squamous cell carcinoma.
Highlights
Fibroblast growth factor receptor 3 (FGFR3) is a cell membrane-bound tyrosine kinase receptor belonging to the fibroblast growth factor receptor family (FGFR1-4) [1]
FGFR3 protein appeared to be frequently overexpressed in both Oral squamous cell carcinoma (OSCC) and OPSCC, and FGFR3 mRNA was found to be upregulated in head and neck squamous cell carcinoma (HNSCC) from the The Cancer Genome Atlas (TCGA) Research Network
Upregulated FGFR3 mRNA levels may account for the overexpression of FGFR3 protein in a minor subset of FGFR3-overexpressed OSCC
Summary
Fibroblast growth factor receptor 3 (FGFR3) is a cell membrane-bound tyrosine kinase receptor belonging to the fibroblast growth factor receptor family (FGFR1-4) [1]. Upon binding of specific FGF ligands, the receptor is phosphorylated and multiple downstream signaling pathways are activated Among these pathways are the mitogen-activated protein kinase (MAPK), (phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), phosphoinositide phospholipase C (PLCγ) and signal transducer and activator of transcription (STAT) signaling pathways [2]. Oncogenic aberrations of the FGFR3 gene cause sustained cell proliferation, contributing to tumor. Inhibiting FGFR3 protein with FGFR3-d irected therapies caused remarkable antitumor effects in preclinical models on brain cancer, colorectal cancer, and multiple myeloma, as well as in clinical trials on glioblastoma patients with tumors bearing FGFR3-TACC3 fusions [3, 4, 6]. Early phase clinical trials are conducted with FGFR3-d irected targeted therapies on patients with FGFR3-aberrated glioblastoma multiforme, transitional cell carcinoma, multiple myeloma, and other advanced solid malignancies (ClinicalTrials.gov Identifier: NCT01975701, NCT02278978, NCT02401542, NCT02052778)
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