Streit S, Mestel D S, Schmidt M, Ullrich A, Berking C
Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Br J Cancer. 2006 Jun 19;94(12):1879-86. doi: 10.1038/sj.bjc.6603181. Epub 2006 May 23.
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.
FGFR4基因（-Arg388）中的单核苷酸多态性与多种人类癌症的进展相关。尽管成纤维细胞生长因子（FGFs）是黑色素瘤中最重要的生长因子之一，但FGF受体亚型4的表达尚未得到研究。在本研究中，通过免疫组织化学分析了137例不同进展阶段黑色素瘤组织中该受体的蛋白表达。45%的标本中表达了FGFR4蛋白，且与pTNM肿瘤分期（UICC，P = 0.023；AJCC，P = 0.046）、微溃疡的存在（P = 0.009）、肿瘤血管生成（P = 0.001）、转移（P = 0.025）、原发肿瘤数量（P = 0.022）、总生存期（P = 0.047）和无病生存期（P = 0.024）相关。此外，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析了185例黑色素瘤患者的FGFR4 Arg388多态性。45%的黑色素瘤患者检测到Arg388等位基因，且与肿瘤厚度（根据Clark浸润水平，P = 0.004；根据Breslow毫米数，P = 0.02）以及肿瘤亚型结节性黑色素瘤（P = 0.002）显著相关。然而，FGFR4 Arg388等位基因与总生存期和无病生存期无相关性。总之，FGFR4的Arg388基因型和蛋白表达可能是黑色素瘤进展的潜在标志物。
