title: FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients.
abstract: A single nucleotide polymorphism in the gene for FGFR4 (-Arg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P = 0.023 and AJCC, P = 0.046), presence of microulceration (P = 0.009), tumour vascularity (P = 0.001), metastases (P = 0.025), number of primary tumours (P = 0.022), overall survival (P = 0.047) and disease-free survival (P = 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P = 0.004) and by Breslow in mm (P = 0.02)) and the tumour subtype nodular melanoma (P = 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.
authors.affiliation: Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Streit
authors.forename: D S
authors.initials: DS
authors.lastname: Mestel
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
authors.forename: C
authors.initials: C
authors.lastname: Berking
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4