Insights into the impact of chromosome 3p mutations in advanced renal cell carcinoma treated with immune-based combinations or targeted therapy: A single-center experience

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-04-09 DOI:10.1016/j.prp.2025.155964

Matteo Rosellini , Veronica Mollica , Andrea Marchetti , Sara Coluccelli , Francesca Giunchi , Elisa Tassinari , Linda Danielli , Thais Maloberti , Costantino Ricci , Michelangelo Fiorentino , Dario de Biase , Francesco Massari

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引用次数: 0

Abstract

Background

Immune-based combinations have transformed first-line treatment for metastatic renal cell carcinoma (mRCC), but reliable biomarkers for patient selection remain elusive. Chromosome 3p mutations (e.g., VHL, PBRM1, SETD2, BAP1) have shown inconsistent prognostic and predictive value. This retrospective study assessed the prognostic impact of tissue-based biomarkers, focusing on 3p mutations in mRCC.

Patients and methods

A single-center retrospective analysis included mRCC patients treated with immunocombinations or tyrosine kinase inhibitors (TKIs). We evaluated mutations in 14 genes, including VHL, PBRM1, SETD2, and BAP1. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Prognostic factors were analyzed using univariate and multivariate models.

Results

Among the included 38 patients, the most common mutations were in VHL (45 %), PBRM1 (42 %), and SETD2 (26 %), with these latter more frequent in males (p = 0.012). Most patients (74 %) received immune-based combinations; 26 % received TKIs. SETD2 mutations were associated with primary refractoriness (30 %). Median OS was not reached; brain metastases (p = 0.001) and BAP1 mutations (p = 0.025) predicted worse OS, while PBRM1 mutations trended toward improved OS (p = 0.845). Median PFS was 14.1 months. Higher tumor grade (p = 0.038) and worse ECOG PS (p = 0.008) negatively impacted PFS, while 3p mutations showed no significant effect on PFS.

Conclusions

ECOG PS and brain metastases were confirmed as poor prognostic factors. VHL and PBRM1 mutations may suggest a better prognosis, while SETD2 and BAP1 mutations portend worse outcomes. Larger studies are needed to confirm these findings.

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染色体3p突变对晚期肾细胞癌免疫联合治疗或靶向治疗的影响：单中心经验

背景：以免疫为基础的联合治疗已经改变了转移性肾细胞癌（mRCC）的一线治疗方法，但可靠的生物标志物选择患者仍然难以捉摸。染色体3p突变（如VHL、PBRM1、SETD2、BAP1）的预后和预测价值不一致。这项回顾性研究评估了基于组织的生物标志物对预后的影响，重点关注mRCC中的3p突变。患者和方法单中心回顾性分析包括接受免疫联合治疗或酪氨酸激酶抑制剂（TKIs）治疗的mRCC患者。我们评估了14个基因的突变，包括VHL、PBRM1、SETD2和BAP1。主要终点是总生存期（OS）和无进展生存期（PFS）。采用单因素和多因素模型分析预后因素。结果在38例患者中，最常见的突变是VHL（45 %）、PBRM1（42 %）和SETD2(26 %)，后者在男性中更常见（p = 0.012）。大多数患者（74% %）接受免疫联合治疗；26% %接受tki治疗。SETD2突变与原发性难治性相关（30% %）。中位OS未达到；脑转移（p = 0.001）和BAP1突变（p = 0.025）预示着更差的OS，而PBRM1突变倾向于改善OS （p = 0.845）。中位PFS为14.1个月。较高的肿瘤分级（p = 0.038）和较差的ECOG PS （p = 0.008）负向影响PFS，而3p突变对PFS无显著影响。结论secog - PS和脑转移是不良预后因素。VHL和PBRM1突变可能预示着更好的预后，而SETD2和BAP1突变预示着更差的预后。需要更大规模的研究来证实这些发现。

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.