FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Abstract

IntroductionFibroblast 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.MethodsProtein 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.ResultsFGFR 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).ConclusionFGFR 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s40291-016-0204-5) contains supplementary material, which is available to authorized users.

Prognostic implications of Fibroblast growth factor receptor 1 (FGFR1) gene amplification and protein overexpression in hypopharyngeal and laryngeal squamous cell carcinoma

“…However, FGFR1 protein overexpression showed no effect on survival outcomes. Previous studies have shown a disagreement with prognostic values of FGFR1 overexpression in HNSCC, probably owing to the use of different FGFR1 overexpression criteria, anti-FGFR1 antibodies, and cohorts with different anatomical locations [13,17,37]. FGFR1 demonstrated strong and diffused expression in poorly differentiated SCC, while normal, dysplastic squamous epithelium, or well differentiated SCC exhibited weak to moderate expression patterns.…”

“…These aberrant FGFR1 alterations, in general, lead to gain-offunction characteristics and constitutively activate the downstream RAS/mitogen-activated protein kinase (MAPK), PI3K/protein kinase B (AKT), and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways [11]. In previous studies of HNSCC, FGFR1 amplification has been reported in 3 to 17% of cases, and FGFR1 protein overexpression has been identified in about 11-82% of cases [12][13][14][15][16][17][18]. However, they presented conflicting results for FGFR1 as a prognostic biomarker.…”

“…However, they presented conflicting results for FGFR1 as a prognostic biomarker. In addition, most of the studies have been conducted on the whole HNSCCs showing biological heterogeneity, and site-specific studies have been rarely performed on SCC, especially in SCCs of hypopharynx and larynx, which represent the prevalent subsites of HPV-negative SCC [13][14][15][16][17][18][19]. Therefore, more evidence is needed for the prognostic or predictive role of FGFR1 in HNSCC of hypopharynx and larynx.…”

Expression of FGF‐2/FGFR‐1 in normal mucosa, salivary gland, preneoplastic, and neoplastic lesions of the oral cavity

“…FGFR1 gene amplification is considered a prognostic marker in HNSCC and might be a potential therapeutic target for patients with oral cancer in the future. Although nonselective tyrosine kinase inhibitors cause several adverse effects, selective FGFR‐inhibitors have already shown therapeutic value in HNSCC cell lines …”

Bioinformatics analysis of the expression and role of microRNA-221-3p in the head and neck squamous cell carcinoma

“…Head and neck squamous cell carcinoma (HNSCC)encompassing the oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and laryngeal squamous cell carcinoma is the sixth most common cancer worldwide, accounting for approximately 1-2% of all cancer deaths, with about 600,000 detection of new cases each year globally [1,2,3].The treatment of patients at the early stage is relatively successful, but the overall survival rate of recurrent or metastatic HNSCC remains low and has barely seen any improvements in their survival for decades [4,5]. Although the past three decades have seen several improvements in the diagnostic tools and treatment regimens, the overall survival rate for the advanced (stage Ⅲ-Ⅳ) head and neck squamous cell carcinoma (HNSCC) is only 65% [6,7]. The current standard of care for such patients are surgery along with radiation and chemotherapy, but these have not significantly improved the 5year survival of the HNSCC patients.…”