FGFR3 mutations and a normal CK20 staining pattern define low-grade noninvasive urothelial bladder tumours

van Oers, Johanna M. M. and Wild, Peter J. and Buryer, Maximilian and Denzinger, Stefan and Stoehr, Robert and Rosskopf, Elke and Hofstaedter, Ferdinand and Steyerberg, Ewout W. and Klinkhammer-Schalke, Monika and Zwarthoff, Ellen C. and van der Kwast, Theodorus H. and Hartmann, Arndt (2007) FGFR3 mutations and a normal CK20 staining pattern define low-grade noninvasive urothelial bladder tumours. EUROPEAN UROLOGY, 52 (3). pp. 760-768. ISSN 0302-2838,

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Abstract

Objectives: Molecular markers superior to conventional clinicopathologic parameters are needed to predict disease courses in bladder cancer patients. In this study, we investigated four markers (Ki-67, TP53, CK20, FGFR3) in primary urothelial bladder tumours and compared them with traditional pathologic features. Methods: Tissue microarrays were used to analyse CK20, TP53, and Ki-67 expression immunohistochemically in 255 unselected patients. FGFR3 mutations were detected by SNaPshot analysis. Results: Abnormal CK20 expression was strongly associated with higher tumour grades and stages (p < 0.001); however, 65% of pTa tumours revealed an abnormal CK20 pattern. In the group of pTaG1 tumours, 59% presented with an abnormal CK20 pattern, whereas 82% carried the FGFR3 mutation. In the group of bladder tumours with normal CK20 pattern, the FGFR3 gene was mutated in 89%, whereas a mutated FGFR3 gene was found in only 37% of cases with abnormal CK20 expression (p < 0.001). All markers proved to be strong predictors of disease-specific survival in univariate studies. However, in multivariate analyses they were not independent from classical pathologic parameters. None of the molecular markers was significantly associated with tumour recurrence. Conclusions: Dysregulation of CK20 expression is an early event in the carcinogenesis of papillary noninvasive bladder cancer, but occurs later than FGFR3 mutations. The group of low-grade noninvasive papillary tumours is defined by the presence of an FGFR3 mutation and a normal CK20 expression pattern. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: GROWTH-FACTOR RECEPTOR-3; TRANSITIONAL-CELL CARCINOMAS; IN-SITU; CYTOKERATIN-20 EXPRESSION; PROLIFERATION INDEX; PREDICT RECURRENCE; CANCER; P53; CLASSIFICATION; PROGNOSIS; bladder cancer; CK20; FGFR3; Ki-67; molecular markers; TP53
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Medicine > Lehrstuhl für Urologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 01 Dec 2020 12:01
Last Modified: 08 Apr 2021 05:21
URI: https://pred.uni-regensburg.de/id/eprint/32276

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