title: Increased angiogenesis and FGFR protein expression indicate a favourable prognosis in bladder cancer.
abstract: 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.
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Krankenhausstrasse 8-10, 91054, Erlangen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Bertz
authors.forename: Christine
authors.initials: C
authors.lastname: Abeé
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwarz-Furlan
authors.forename: Joachim
authors.initials: J
authors.lastname: Alfer
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstädter
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Andreas K A
authors.initials: AK
authors.lastname: Gaumann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D051498:Receptor, Fibroblast Growth Factor, Type 3