Prognostic impact of combined loss of RB1, p53 and p21 in muscle-invasive bladder cancer

Ebner, Benedikt ; Eismann, Lennert; Hermans, Julian; Kidess, Marc; Pyrgidis, Nikolaos ; Semmler, Marie; Volz, Yannic ; Buchner, Alexander ; Chaloupka, Michael ; Eich, Marie-Lisa; Weinhold, Philipp ; Stief, Christian G. ; Horst, David; Schulz, Gerald B. und Schallenberg, Simon (June 2025): Prognostic impact of combined loss of RB1, p53 and p21 in muscle-invasive bladder cancer. In: Pathology - Research and Practice, Vol. 270, 155960

Abstract

Introduction

Muscle-invasive bladder cancer (MIBC) represents a genetically heterogeneous disease with limited prognostic markers. This study aimed to validate the prognostic relevance of combined alterations in cell cycle regulators RB1, p53, and p21 in a broad cohort of MIBC patients undergoing radical cystectomy (RC).

Material and Methods

We analyzed formalin-fixed paraffin-embedded material from MIBC patients who underwent RC at the Department of Urology, University Hospital, Ludwig-Maximilians-University Munich. Tissue microarrays (TMAs) from 251 MIBC patients (pT2-pT4) were constructed, incorporating triplicate cores from tumor center and front. Immunohistochemical expression of RB1, p53, and p21 was assessed using a four-grade scoring system. Prognostic associations with overall survival (OS) and cancer-specific survival (CSS) were evaluated using multivariable Cox regression, Kaplan-Meier curves, and log-rank tests.

Results

We assessed 4518 stainings from 251 patients. Single marker analysis revealed no significant association between the loss of RB1, p53, or p21 and OS or CSS. However, the loss of two or three markers was significantly associated with worse OS (HR 3.49, 95 % CI 1.28–9.50; p = 0.01) and CSS (HR 11.2, 95 % CI 1.46–86.04; p = 0.02).

Conclusions

RB1, p53, and p21 are insufficient as single prognostic markers in MIBC but demonstrate significant prognostic relevance when analyzed in combination. These findings underscore the need for multi-marker approaches in prognostic modeling and personalized treatment strategies for MIBC.

• Item Type: Journal article
• Faculties: Medicine > Institute of Pathology; Medicine > Medical Center of the University of Munich > Urology Clinic and Polyclinic
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 03440338
• Language: English