Integrated assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry.

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2024-09-23 DOI:10.1111/neup.13005
Kenta Masui, Hiromi Onizuka, Yoshihiro Muragaki, Takakazu Kawamata, Yoji Nagashima, Atsushi Kurata, Takashi Komori
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Abstract

In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the "routine diagnostics" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries. We herein validated the usefulness of p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as potential surrogates for the assessment of CDKN2A status in 20 IDH-mutant astrocytoma cases. Of note, loss or retention of p16 and MTAP could accurately predict CDKN2A HD (p16: 87.5%, MTAP: 88.9%) or non-HD (p16: 100%, MTAP: 100%) with a single marker alone. Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.

利用 p16 和甲硫腺苷磷酸酶免疫组化综合评估 IDH 突变星形细胞瘤的恶性程度。
在世界卫生组织(WHO)第五版中枢神经系统(CNS)肿瘤分类中,分子分析不仅是确定每种肿瘤类型的必要条件,也是根据恶性程度(CNS WHO 分级)评估预后的必要条件。一个显著的例子是肿瘤抑制基因细胞周期蛋白依赖性激酶抑制剂 2A(CDKN2A)的缺失,CDKN2A 基因同源缺失(HD)是异柠檬酸脱氢酶基因(IDH)突变星形细胞瘤的新型中枢神经系统 WHO 4 级标志物。然而,将分子检查纳入每种脑肿瘤类型的 "常规诊断 "仍是一项重大挑战,尤其是在资源有限的环境中,包括低收入和中等收入国家。我们在此验证了在20例IDH突变星形细胞瘤病例中,p16和甲硫腺苷磷酸化酶(MTAP)免疫组化(IHC)作为评估CDKN2A状态的潜在替代物的实用性。值得注意的是,p16 和 MTAP 的缺失或保留可准确预测 CDKN2A HD(p16:87.5%,MTAP:88.9%)或非 HD(p16:100%,MTAP:100%)。重要的是,我们揭示了导致灰区 IHC 结果(p16:5-20%,MTAP:镶嵌)的因素,包括(1)CDKN2A 的半杂合子缺失,(2)变性结果,以及(3)瘤内 CDKN2A HD 异质性,对其进行详细的组织学和分子评估将是实现 IDH 突变星形细胞瘤恶性综合评估的关键。我们总结了每种方法的误区,并首次提供了星形细胞瘤分级的实用流程图,有助于在资源有限的环境中实现基于WHO2021的分子诊断正常化。
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
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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