MTAP免疫组化作为脑肿瘤中CDKN2A缺失的替代标志物:一项荟萃分析与文献综述

MTAP immunohistochemistry as a surrogate marker of CDKN2A loss in brain tumors: A meta-analysis and literature review.

作者信息

Dono Antonio, Pichardo-Rojas Diego, Mendoza Mora Leonardo, Pichardo-Rojas Pavel S, Marin-Castañeda Luis A, Carrillo Abril, Coria Medrano Adrian, Esquenazi Yoshua, Ballester Leomar Y

机构信息

Vivian L. Smith Department of Neurosurgery, The University of Texas, Health Science Center at Houston, Houston, TX, United States.

Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.

出版信息

J Neuropathol Exp Neurol. 2025 Apr 18. doi: 10.1093/jnen/nlaf033.

Abstract

Given the known relationship between CDKN2A homozygous deletion (HD) and worsened outcomes in both meningiomas and IDH-mutant astrocytomas, it is paramount to identify CDKN2A HD for accurate risk stratification of patients. Multiple array platforms can detect CDKN2A HD. However, these methods are expensive and are not readily available at every institution. To address this, we conducted a meta-analysis and literature review to evaluate 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A HD. Our study analyzed 7 cohort studies, 3 of which focused on meningiomas encompassing a total of 87 patients; and 4 studies were conducted on infiltrating glioma patients, consisting of 423 patients. Our results show that despite utilizing different MTAP IHC clones, the results among all studies showed consistently good sensitivity and specificity. The overall sensitivity and specificity of MTAP IHC as a surrogate of CDKN2A HD was excellent with 92.3% and 97.5%, respectively. These results were maintained when MTAP IHC was evaluated in distinct tumor types. MTAP IHC is a good surrogate marker for identifying CDKN2A HD in infiltrating gliomas and meningiomas. MTAP IHC implementation would allow correct integrated diagnosis for institutions that lack DNA sequencing.

摘要

鉴于已知CDKN2A纯合缺失(HD)与脑膜瘤和异柠檬酸脱氢酶(IDH)突变型星形细胞瘤预后恶化之间的关系,识别CDKN2A HD对于准确进行患者风险分层至关重要。多种基因芯片平台可检测CDKN2A HD。然而,这些方法成本高昂,并非每个机构都能轻易获得。为解决这一问题,我们进行了一项荟萃分析和文献综述,以评估通过免疫组织化学(IHC)测定的5'-甲硫腺苷磷酸化酶(MTAP)表达作为CDKN2A HD的替代指标。我们的研究分析了7项队列研究,其中3项聚焦于脑膜瘤,共纳入87例患者;4项研究针对浸润性胶质瘤患者,共423例。我们的结果表明,尽管使用了不同的MTAP IHC克隆,但所有研究的结果均显示出一致良好的敏感性和特异性。MTAP IHC作为CDKN2A HD替代指标的总体敏感性和特异性分别为92.3%和97.5%,非常出色。在不同肿瘤类型中评估MTAP IHC时,这些结果保持不变。MTAP IHC是识别浸润性胶质瘤和脑膜瘤中CDKN2A HD的良好替代标志物。对于缺乏DNA测序的机构,实施MTAP IHC将有助于进行正确的综合诊断。

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