title: Involvement of the FGFR4 Arg388 allele in head and neck squamous cell carcinoma.
abstract: Fibroblast growth factor receptors (FGFRs) have been implicated in various forms of human hyperproliferative disorders such as cancers of the cervix and bladder. We investigated the expression pattern of FGFR4 and the clinical significance of the recently identified Gly/Arg polymorphism (388) in head and neck squamous cell carcinomas (HNSCCs) of the oral cavity and the oropharynx. Sections from 104 paraffin-embedded tumors were analyzed by a restriction fragment length polymorphism-based method to determine the FGFR4 genotypes. Protein expression was investigated immunohistochemically and graded into a low, intermediate, or high degree of staining. FGFR4 expression was scored as high in 17, as intermediate in 59 and as low in 28 cases. The FGFR4 Arg388 allele was found in 59 tumors, 46 of them having heterozygous and 13 homozygous genotypes. High expression of the FGFR4 Arg388 allele was significantly associated with reduced overall survival (p = 0.032) and with an advanced tumor stage (p = 0.023), whereas expression of the FGFR4 Gly388 had no impact on disease progression. Our findings indicate that high expression of FGFR4 in connection with the Arg388 allele is associated with poor clinical outcome and support the significance of FGFR4 as a diagnostic marker and a target for therapeutic intervention in human HNSCC.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Streit
authors.forename: Johannes
authors.initials: J
authors.lastname: Bange
authors.forename: Alexander
authors.initials: A
authors.lastname: Fichtner
authors.forename: Stephan
authors.initials: S
authors.lastname: Ihrler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Issing
authors.forename: Axel
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D005346:Fibroblast Growth Factors; D020869:Gene Expression Profiling; D005819:Genetic Markers; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D005819:Genetic Markers; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4