title: Positive fibroblast growth factor receptor 3 immunoreactivity is associated with low-grade non-invasive urothelial bladder cancer.
abstract: In addition to conventional clinicopathological parameters, molecular markers are also required in order to predict the course of disease in patients with urothelial bladder cancer (BC). Little is known about fibroblast growth factor receptor 3 (FGFR3) immunoreactivity and the clinical significance it may possess with regard to BC. The present study aimed to investigate the immunoreactivity of FGFR3 in primary urothelial bladder tumours, with regard to clinicopathological features andFGFR3mutation status. Tissue microarrays were used to immunohistochemically analyseFGFR3expression in 255 primary, unselected patients with BC.FGFR3mutations were detected using SNaPshot analysis. Positive FGFR3 immunoreactivity was identified in 113/207 analysable cases (54.6%), and was significantly associated withFGFR3mutation (P<0.001), low tumour stage (P<0.001), low histological grade (P<0.001) and a papillary growth pattern (P<0.001). Positive FGFR3 immunostaining (P=0.002) and FGFR3 mutation (P=0.002) were found to be significantly associated with increased disease-specific survival following univariate analysis, demonstrating a median follow-up period of 75 months. Using multivariate analyses, FGFR3 immunoreactivity was found not to be independent of classical pathological parameters. Immunohistochemical expression of FGFR3 is an early occurrence during the carcinogenesis of papillary non-invasive BC. The presence of FGFR3 immunoreactivity in non-invasive papillary urothelial carcinomas may be utilised as an indicator of tumours possessing low-grade features and good prognosis.
authors.affiliation: Department of Urology, University Hospital Zurich, University of Zurich, Zurich CH-8091, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Poyet
authors.affiliation: Department of Urology, University Hospital Zurich, University of Zurich, Zurich CH-8091, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermanns
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, Zurich CH-8091, Switzerland.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Department of Urology, University Hospital Zurich, University of Zurich, Zurich CH-8091, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Drescher
authors.affiliation: Department of Urology, University Hospital Zurich, University of Zurich, Zurich CH-8091, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eberli
authors.affiliation: Department of Urology, University Hospital Regensburg, Regensburg 93059, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg 93059, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.affiliation: Institute of Pathology, University of Erlangen, Erlangen 91054, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Institute of Pathology, University of Erlangen, Erlangen 91054, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Stöhr
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam 3015, The Netherlands.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.affiliation: Department of Urology, University Hospital Zurich, University of Zurich, Zurich CH-8091, Switzerland.
authors.forename: Tullio
authors.initials: T
authors.lastname: Sulser
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, Zurich CH-8091, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
keywords: fibroblast growth factor receptor 3 protein; grading; molecular markers; prognosis; urothelial cancer