van Rhijn, Bas W. G. and Mertens, Laura S. and Mayr, Roman and Bostrom, Peter J. and Real, Francisco X. and Zwarthoff, Ellen C. and Boormans, Joost L. and Abas, Cheno and van Leenders, Geert J. l H. and Gotz, Stefanie and Hippe, Katrin and Bertz, Simone and Neuzillet, Yann and Sanders, Joyce and Broeks, Annegien and van der Heijden, Michiel S. and Jewett, Michael A. S. and Marquez, Mirari and Stoehr, Robert and Zlotta, Alexandre R. and Eckstein, Markus and Soorojebally, Yanish and Roshani, Hossain and Burger, Maximilian and Otto, Wolfgang and Radvanyi, Francois and Sirab, Nanor and Pouessel, Damien and Wullich, Bernd and van der Kwast, Theo H. and Malats, Nuria and Hartmann, Arndt and Allory, Yves and Zuiverloon, Tahlita C. M. (2020) FGFR3 Mutation Status and FGFR3 Expression in a Large Bladder Cancer Cohort Treated by Radical Cystectomy: Implications for Anti-FGFR3 Treatment? EUROPEAN UROLOGY, 78 (5). pp. 682-687. ISSN 0302-2838, 1873-7560
Full text not available from this repository. (Request a copy)Abstract
Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer (BC). FGFR3 mutations are common in noninvasive BC and associated with favorable BC prognosis. Overexpression was reported in up to 40% of FGFR3 wild-type muscle-invasive BC. We analyzed FGFR3 mutations, FGFR3, and p53 protein expression and assessed their prognostic value in a cohort of 1000 chemotherapy-naive radical cystectomy specimens. FGFR3 mutations were found in 11%, FGFR3 overexpression was found in 28%, and p53 overexpression was found in 69% of tumors. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression versus 22% among FGFR3 wild-type tumors. FGFR3 mutations were significantly associated with lower pT stage, tumor grade, absence of carcinoma in situ, pN0, low-level p53, and longer disease-specific survival (DSS). FGFR3 overexpression was associated only with lower pT stage and tumor grade. Moreover, FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. In conclusion, FGFR3 mutations identified patients with favorable BC at cystectomy. Our results suggest that FGFR3 mutations have a driver role and are functionally distinct from FGFR3 overexpression. Hence, patients with FGFR3 mutations would be more likely to benefit from anti-FGFR3 therapy. Ideally, further research is needed to test this hypothesis. Patient summary: Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations are very common in bladder cancer. In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DOVITINIB; TRIAL; Bladder; Cancer; Urothelial carcinoma; Cystectomy; FGFR3; Expression; Mutation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 11:33 |
| Last Modified: | 08 Mar 2021 11:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43488 |
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