腹膜间皮瘤的分子特征。
Molecular Characterization of Peritoneal Mesotheliomas.
机构信息
Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
出版信息
J Thorac Oncol. 2022 Mar;17(3):455-460. doi: 10.1016/j.jtho.2021.09.012. Epub 2021 Oct 11.
INTRODUCTION
Malignant peritoneal mesothelioma (MPeM) is clinically distinct and less studied than malignant pleural mesothelioma. We report the genomic and immunophenotypic features of a prospectively collected MPeM cohort.
METHODS
Next-generation sequencing (NGS) was performed on MPeM tumors. Genomic near-haploidization (GNH) was assessed. WT1, BAP1, mesothelin, VISTA, and programmed death-ligand 1 were evaluated by immunohistochemistry (IHC) when tissue was available. Overall survival was stratified by selected genomic and IHC features.
RESULTS
A total of 50 consented patients with MPeM (45 epithelioid, 5 nonepithelioid) were studied exhibiting common alterations in BAP1 (60%; 30 of 50), NF2 (24%; 12 of 50) SETD2 (22%; 11 of 50), and TP53 (16%; 8 of 50). A total of 76% (38 of 50) of specimens were assessable for allele-specific copy number analysis; 8% (3 of 38) had GNH. IHC positivity rates were 93% (37 of 40) for mesothelin, 96% (46 of 48) for WT1, 50% (19 of 38) for programmed death-ligand 1, and 89% (34 of 38) for VISTA. BAP1 loss by IHC was observed in 76% (29 of 38), including five wild-type on NGS. Combining NGS and IHC for BAP1, overall survival was worse with alteration or loss compared with wild-type or retained in all patients (n = 37 versus 13, 43.8 versus 117.3 mo, p = 0.04) Three of 30 patients had a pathogenic germline variant: POT1 I78T, MUTYH R109Y, and BAP1 E402∗.
CONCLUSIONS
MPeM has distinct biology and genomic composition. CDKN2A/B alterations were rare in MPeM, whereas BAP1, NF2, TP53, SETD2, and LATS2 were common. BAP1 alteration/loss was associated with shorter survival when all patients were included. A notable minority of specimens had GNH associated with NF2, TP53, and SETDB1 mutations. Pathogenic germline mutations were found in 3 of 30 patients.
简介
恶性腹膜间皮瘤（MPeM）在临床上与恶性胸膜间皮瘤不同，研究也较少。我们报告了一组前瞻性收集的 MPeM 队列的基因组和免疫表型特征。
方法
对 MPeM 肿瘤进行下一代测序（NGS）。评估基因组近单体性（GNH）。当组织可用时，通过免疫组织化学（IHC）评估 WT1、BAP1、间皮素、VISTA 和程序性死亡配体 1。根据选定的基因组和 IHC 特征对总生存期进行分层。
结果
共研究了 50 名同意的 MPeM 患者（45 名上皮样，5 名非上皮样），常见的改变包括 BAP1（60%；50 例中有 30 例）、NF2（24%；50 例中有 12 例）、SETD2（22%；50 例中有 11 例）和 TP53（16%；50 例中有 8 例）。总共 76%（50 例中有 38 例）的标本可用于等位基因特异性拷贝数分析；8%（38 例中有 3 例）存在 GNH。IHC 阳性率为 93%（40 例中有 37 例）为间皮素，96%（48 例中有 46 例）为 WT1，50%（38 例中有 19 例）为程序性死亡配体 1，89%（38 例中有 34 例）为 VISTA。IHC 观察到 BAP1 缺失率为 76%（38 例中有 29 例），包括 5 例 NGS 野生型。在所有患者中（n=37 与 13，43.8 与 117.3 mo，p=0.04），将 NGS 和 IHC 联合用于 BAP1 时，与野生型或保留相比，改变或缺失的总体生存率更差。30 例患者中有 3 例有致病性种系变异：POT1 I78T、MUTYH R109Y 和 BAP1 E402∗。
结论
MPeM 具有独特的生物学和基因组组成。CDKN2A/B 改变在 MPeM 中罕见，而 BAP1、NF2、TP53、SETD2 和 LATS2 则很常见。当包括所有患者时，BAP1 改变/缺失与较短的生存期相关。少数标本存在与 NF2、TP53 和 SETDB1 突变相关的 GNH。在 30 名患者中发现了致病性种系突变。
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