Immune checkpoint markers and tumour mutation burden in Wilms tumour: a study of 59 cases

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology Pub Date : 2024-05-21 DOI:10.1016/j.pathol.2024.03.005

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引用次数: 0

Abstract

Wilms tumour (WT) is the most common renal tumour in children, and studies of immune checkpoint inhibitors (ICIs) treatment and markers are limited in number. In this study we investigated the ICIs' related immune landscape by examining the expression of PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) proteins by immunohistochemistry (IHC), tumour mutation burden (TMB), and correlations with histology and clinical outcome. Positive PD-L1 (SP263) expression was defined as modified combined positive score (CPS) ≥1. A total of 59 WTs (from 2000 to 2017), including eight (14.0%) with anaplasia, from 46 patients were analysed (45 primary and 14 metastatic). Thirteen WTs (13/59, 22%) were positive for PD-L1 (8 primary, 5 metastatic; CPS 1.11–3.42). Positive PD-L1 expression was associated with diffuse anaplasia (p<0.05) and significantly shorter progression-free survival (p<0.05) among WTs with favourable histology (n=39). CD8+ lymphocytes were present in all analysed WTs. A subset of CD8+ cells co-expressed PD-1, which was associated with favourable histology and treatment. MMR IHC stains identified two (2/18, 11%) WTs with isolated PMS2 loss. All six WTs analysed for TMB showed low mutation burden. We found CD8+ lymphocytes in all analysed WTs and identified a fraction of WT (17.8% of primary and 35.8% of metastatic) with positive PD-L1 CPS, suggesting potential response to ICIs in some patients.

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Wilms 肿瘤中的免疫检查点标记物和肿瘤突变负荷：对 59 个病例的研究

Wilms瘤（WT）是儿童最常见的肾脏肿瘤，而有关免疫检查点抑制剂（ICIs）治疗和标记物的研究数量有限。在这项研究中，我们通过免疫组化（IHC）检测了PD-L1、PD-1、CD8和DNA错配修复（MMR）蛋白的表达、肿瘤突变负荷（TMB）以及与组织学和临床结果的相关性，从而研究了ICIs的相关免疫情况。共分析了 46 名患者（45 名原发性患者和 14 名转移性患者）的 59 例 WT（2000 年至 2017 年），其中包括 8 例（14.0%）增生性肿瘤。13例WT（13/59，22%）PD-L1阳性（8例原发性，5例转移性；CPS 1.11-3.42）。PD-L1 阳性表达与弥漫性增生（p<0.05）和组织学良好的 WTs（n=39）无进展生存期显著缩短（p<0.05）有关。CD8+ 淋巴细胞存在于所有分析的 WTs 中。CD8+细胞的一个亚群共同表达PD-1，这与良好的组织学和治疗有关。MMR IHC染色发现两个（2/18，11%）WTs有孤立的PMS2缺失。对所有六例WT进行的TMB分析均显示出较低的突变负荷。我们在所有分析的 WT 中都发现了 CD8+ 淋巴细胞，并发现部分 WT（17.8% 的原发性 WT 和 35.8% 的转移性 WT）的 PD-L1 CPS 呈阳性，这表明部分患者可能会对 ICIs 产生反应。

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来源期刊

Pathology 医学-病理学

CiteScore

6.50

自引率

2.20%

发文量

459

审稿时长

54 days

期刊介绍： Published by Elsevier from 2016 Pathology is the official journal of the Royal College of Pathologists of Australasia (RCPA). It is committed to publishing peer-reviewed, original articles related to the science of pathology in its broadest sense, including anatomical pathology, chemical pathology and biochemistry, cytopathology, experimental pathology, forensic pathology and morbid anatomy, genetics, haematology, immunology and immunopathology, microbiology and molecular pathology.