Fibroblast Growth Factor Receptor Family Members as Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review

Abstract

BackgroundSince head and neck cancer is characterized by poor survival rates, there is a demand for novel therapeutic targets and prognostic biomarkers. An upcoming therapeutic target is the fibroblast growth factor receptor (FGFR) family. However, their prognostic role in head and neck cancer remains unclear.ObjectiveTo systematically review current evidence on the prognostic value of FGFR family members in head and neck squamous cell carcinoma (HNSCC).MethodsA systematic search of PubMed, Embase, and the Cochrane Library was performed for publications up to 14 May 2014. Two reviewers screened all articles and included prognostic studies on the molecular biomarkers FGFR1-5 in any type of HNSCC. Relevant studies were assessed on risk of bias using the Quality in Prognostic Studies (QUIPS) tool. Data on FGFR aberrations and survival outcome were extracted from relevant studies. The prognostic value of FGFR aberrations was compared among studies.ResultsThe initial search yielded 1568 publications of which 12 fulfilled the inclusion criteria. Four studies reported FGFR1 gene amplification (9.3–17.4 %) and FGFR1 protein overexpression (11.8 %) in HNSCC. FGFR1 protein expression by cancer-associated fibroblasts correlated with poor survival outcome in one study (p < 0.01). Eight studies reported high rates of FGFR4 Gly388Arg polymorphisms (32.5–54.2 %) and FGFR4 protein overexpression (16–35 %), with varying correlations with survival. So far, no studies assessed the prognostic role of FGFR2, FGFR3, or FGFR5 in HNSCC.LimitationsSignificant risk of bias has been identified among included studies. Therefore, cautious interpretation of the results is recommended.ConclusionIn conclusion, evidence was found for prognostic value of FGFR1 expression in cancer-associated fibroblasts in HNSCC. Prognostic evidence on the other FGFR family members in HNSCC is limited and conflicting. This emphasizes the need for future well-conducted prognostic studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s11523-015-0374-9) contains supplementary material, which is available to authorized users.

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

“…In addition, we observed prognostic value for FGFR1 protein expression in HPV-negative HNSCC, which has not been reported by previous studies, although Hase and colleagues reported prognostic value for FGFR1 expression in oral cancer-associated fibroblast (32,33). These contradictions might be explained by differences in anti-FGFR1 antibodies to determine protein expression or study populations.…”

Prognostic importance of FGF2 and FGFR1 expression for patients affected by ameloblastoma

“…Alternative splicing generates two different isoforms (b/c) of the IgIII domain in each of the receptors, but not in FGFR4. Recently, FGFR5 was described, but with no intracellular tyrosine kinase domain …”

“…The expression of FGF‐FGFR has been shown to be altered in a diverse number of human neoplasms; in many cases, these changes represent important prognostic factors . For odontogenic tumors, few studies attempted to investigate the distribution and importance of these molecules.…”

FGFR4 Is a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma

“…They reported contradicting findings on the prognostic value of FGFR4 protein expression and the FGFR4 Gly388Arg SNP [26]. Regarding overall survival, Streit et al [19] and da Costa Andrade et al [22] related the FGFR4 388Arg allele to poor overall survival, while Ansell et al [23] related it to better overall survival and Azad et al [24] and Choi et al [25] found no relationship.…”