Bertz Simone, Abeé Christine, Schwarz-Furlan Stephan, Alfer Joachim, Hofstädter Ferdinand, Stoehr Robert, Hartmann Arndt, Gaumann Andreas K A
Institute of Pathology, University Hospital Erlangen, Krankenhausstrasse 8-10, 91054, Erlangen, Germany.
Virchows Arch. 2014 Dec;465(6):687-95. doi: 10.1007/s00428-014-1672-9. Epub 2014 Oct 19.
Compared to other members of the fibroblast growth factor receptor (FGFR) family, only few studies investigate FGFR3 in tumour angiogenesis. We investigated the connection between angiogenesis and FGF/FGFR expression including FGFR3 mutation status in urothelial carcinomas. Immunohistochemistry was performed in invasive and non-invasive urothelial cancers of 61 patients. Protein expression of CD31, factor VIII (FVIII), FGF-1/2, FGFR1, FGFR3 and FGFR4 and FGFR3 mutation status were evaluated. Morphometric assessment of angiogenesis including microvessel count (MVC) and vascular surface area (VSA) was analysed. Correlation and survival analyses (overall survival (OS) and disease-free survival (DFS)) with univariate and multivariate analyses were performed. CD31 values (MVC and VSA) significantly correlated with OS and DFS. OS and DFS were significantly better in patients with FGFR3 overexpression. Multivariate analysis revealed FGFR3 protein expression and tumour grading (WHO classification 2004) as independent prognostic factors of OS and VSA of CD31 and FGFR3 protein expression of DFS. FGFR3 mutation status was correlated with VSA measured by FVIII. FGFR3 may be able to induce a pro-angiogenic phenotype in urothelial carcinomas and significantly influence prognosis. Consequently, FGFR3 is a potential therapeutic target also from the angiogenesis perspective.
与成纤维细胞生长因子受体（FGFR）家族的其他成员相比，仅有少数研究调查了FGFR3在肿瘤血管生成中的作用。我们研究了血管生成与FGF/FGFR表达之间的联系，包括FGFR3在尿路上皮癌中的突变状态。对61例患者的浸润性和非浸润性尿路上皮癌进行了免疫组织化学检测。评估了CD31、因子VIII（FVIII）、FGF-1/2、FGFR1、FGFR3和FGFR4的蛋白表达以及FGFR3的突变状态。分析了包括微血管计数（MVC）和血管表面积（VSA）在内的血管生成的形态计量学评估。进行了单因素和多因素分析的相关性和生存分析（总生存（OS）和无病生存（DFS））。CD31值（MVC和VSA）与OS和DFS显著相关。FGFR3过表达的患者的OS和DFS明显更好。多因素分析显示FGFR3蛋白表达和肿瘤分级（2004年WHO分类）是OS以及CD31的VSA和DFS的FGFR3蛋白表达的独立预后因素。FGFR3突变状态与通过FVIII测量的VSA相关。FGFR3可能能够在尿路上皮癌中诱导促血管生成表型并显著影响预后。因此，从血管生成的角度来看，FGFR3也是一个潜在的治疗靶点。
