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

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-04-08 DOI:10.1016/j.prp.2025.155960

Benedikt Ebner , Lennert Eismann , Julian Hermans , Marc Kidess , Nikolaos Pyrgidis , Marie Semmler , Yannic Volz , Alexander Buchner , Michael Chaloupka , Marie-Lisa Eich , Philipp Weinhold , Christian G. Stief , David Horst , Gerald B. Schulz , Simon Schallenberg

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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.

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肌肉浸润性膀胱癌中 RB1、p53 和 p21 联合缺失的预后影响

肌肉侵袭性膀胱癌（MIBC）是一种遗传异质性疾病，预后标志物有限。本研究旨在验证细胞周期调节因子RB1、p53和p21联合改变在接受根治性膀胱切除术（RC）的MIBC患者中的预后相关性。材料和方法我们分析了在慕尼黑路德维希-马克西米利安大学医院泌尿外科接受RC的MIBC患者的福尔马林固定石蜡包埋材料。构建了251例MIBC患者（pT2-pT4）的组织微阵列（TMAs），包括肿瘤中心和前部的三复制核。RB1、p53和p21的免疫组织化学表达采用四级评分系统进行评估。使用多变量Cox回归、Kaplan-Meier曲线和log-rank检验评估预后与总生存期（OS）和癌症特异性生存期（CSS）的相关性。结果我们评估了251例患者的4518个染色。单标记分析显示，RB1、p53或p21的缺失与OS或CSS之间没有显著关联。然而，两个或三个标记物的丢失与更差的OS显著相关(HR 3.49, 95 % CI 1.28-9.50；p = 0.01)和CSS (HR 11.2, 95% % CI 1.46-86.04； = 0.02页)。结论srb1、p53和p21作为MIBC的单一预后指标是不够的，但联合分析时具有显著的预后相关性。这些发现强调了在MIBC的预后建模和个性化治疗策略中需要多标志物方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.