Mertens, Laura S. and Claps, Francesco and Mayr, Roman and Bostrom, Peter J. and Shariat, Shahrokh F. and Zwarthoff, Ellen C. and Boormans, Joost L. and Abas, Cheno and van Leenders, Geert J. L. H. and Goetz, Stefanie and Hippe, Katrin and Bertz, Simone and Neuzillet, Yann and Sanders, Joyce and Broeks, Annegien and Peters, Dennis and van der Heijden, Michiel S. and Jewett, Michael A. S. and Stoehr, Robert and Zlotta, Alexandre R. and Eckstein, Markus and Soorojebally, Yanish and van der Schoot, Deric K. E. and Wullich, Bernd and Burger, Maximilian and Otto, Wolfgang and Radvanyi, Francois and Sirab, Nanour and Pouessel, Damien and van der Kwast, Theo H. and Hartmann, Arndt and Lotan, Yair and Allory, Yves and Zuiverloon, Tahlita C. M. and van Rhijn, Bas W. G. (2022) Prognostic markers in invasive bladder cancer: FGFR3 mutation status versus P53 and KI-67 expression: a multi-center, multi-laboratory analysis in 1058 radical cystectomy patients. UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 40 (3): 110.e1. ISSN 1078-1439, 1873-2496
Full text not available from this repository. (Request a copy)Abstract
Objectives: To determine the association between the FGFR3 mutation status and immuno-histochemistry (IHC) markers (p53 and Ki-67) in invasive bladder cancer (BC), and to analyze their prognostic value in a multicenter, multi-laboratory radical cystectomy (RC) cohort. Patients and methods: We included 1058 cN0M0, chemotherapy-naive BC patients who underwent RC with pelvic lymph-node dissection at 8 hospitals. The specimens were reviewed by uro-pathologists. Mutations in the FGFR3 gene were examined using PCR-SNaPshot; p53 and Ki-67 expression were determined by standard IHC. FGFR3 mutation status as well as p53 (cut-off> 10%) and Ki-67 (cutoff> 20%) expression were correlated to clinicopathological parameters and disease specific survival (DSS). Results: pT-stage was < pT2 in 80, pT2 in 266, pT3 in 513 and pT4 in 199 patients, respectively. Cancer-positive nodes were found in 410 (39%) patients. An FGFR3 mutation was detected in 107 (10%) and aberrant p53 and Ki-67 expression in 718 (68%) and 581(55%) tumors, respectively. The FGFR3 mutation was associated with lower pT-stage (P< 0.001), lower grade (P< 0.001), pN0 (P=0.001) and prolonged DSS (P< 0.001). Aberrant Ki-67 and p53 expression were associated with higher pT-stage and G3-tumors, but not with pN-stage or worse DSS, even if these IHC-biomarkers were combined (P=0.81). Significant predictors for DSS in multivariable analysis were pT-stage (HR1.5, 95%CI:1.3-1.6; P< 0.001), lympho-vascular invasion (LVI) (HR1.4, 95%CI:1.2-1.7; P=0.001), pN-stage (HR1.9, 95%CI:1.6-2.4; P< 0.001) and FGFR3 mutation status (HR1.6, 95%CI:1.1-2.2; P=0.011). Conclusion: The FGFR3 mutation selectively identified patients with favorable BC at RC while p53 and Ki-67 were only associated with adverse tumor characteristics. Our results suggest that, besides tumor-stage, nodal-status and LVI, the oncogenic FGFR3 mutation may represent a valuable tool to guide adjuvant treatment and follow-up strategies after RC. (C) 2021 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR RECEPTOR-3; UROTHELIAL CARCINOMA; CELL-CARCINOMA; ACCUMULATION; GRADE; IMMUNOHISTOCHEMISTRY; PROGRESSION; PREDICTION; Bladder; Cancer; Urothelial carcinoma; Cystectomy; FGFR3; Mutation; Immunohistochemistry; p53; Ki-67 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2024 14:22 |
| Last Modified: | 26 Jan 2024 14:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58234 |
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