在诊断世界卫生组织4级异柠檬酸脱氢酶（IDH）突变型星形细胞瘤中CDKN2A/B状态与形态学的比较：临床相关性是什么？

CDKN2A/B status versus morphology in diagnosing WHO grade 4 IDH-mutated astrocytomas: what is the clinical relevance?

作者信息

Lipatnikova Anna, Kling Teresia, Dénes Anna, Carstam Louise, Corell Alba, Blomstrand Malin, Vega Sandra Ferreyra, Harba Dima, Bontell Thomas Olsson, Carén Helena, Jakola Asgeir S

机构信息

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå stråket 7, Floor 3, Gothenburg, 413 45, Sweden.

Sahlgrenska Center for Cancer Research, Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

J Neurooncol. 2025 May 20. doi: 10.1007/s11060-025-05078-x.

DOI:10.1007/s11060-025-05078-x

PMID:40392514

Abstract

PURPOSE

In the 2021 WHO classification system for central nervous system tumors, the diffuse glioma subgroup IDH-mutated (IDHm) astrocytomas WHO grade 4 was introduced. The diagnosis can be based upon molecular or histopathological morphological criteria. Here we explore whether phenotype and survival of IDHm astrocytomas WHO grade 4 differed across the criteria used for diagnosis.

METHODS

Patients with IDHm astrocytoma, WHO grade 4, were included from Sahlgrenska University Hospital and TCGA database. We created three subgroups based upon the criteria for diagnosis of WHO grade 4; (1) homozygous CDKN2A/B deletion; (2) morphological (necrosis and/or microvascular proliferation); (3) combined subgroup with both homozygous CDKN2A/B deletion and morphological grade 4 criteria.

RESULTS

We included 90 patients (local cohort, n = 35, TCGA cohort, n = 55) with IDHm astrocytoma, WHO grade 4. The median survival was 4.1 years (95% CI 3.0-5.3). Survival was comparable when the diagnosis was based on homozygous CDKN2A/B deletion and on morphological WHO grade 4 criteria (5.2 vs. 5.3 years). However, in the combined subgroup, survival was significantly shorter (2.8 years, p = 0.006).

CONCLUSION

The different subgroups of IDHm astrocytoma WHO grade 4 share similar characteristics. Patients whose tumors exhibit combined criteria have worse prognosis.

摘要

目的

在2021年世界卫生组织中枢神经系统肿瘤分类系统中，引入了弥漫性胶质瘤亚组异柠檬酸脱氢酶突变（IDHm）的4级星形细胞瘤。诊断可基于分子或组织病理学形态学标准。在此，我们探讨4级IDHm星形细胞瘤的表型和生存率在用于诊断的不同标准之间是否存在差异。

方法

从萨尔格伦斯卡大学医院和TCGA数据库纳入4级IDHm星形细胞瘤患者。我们根据4级诊断标准创建了三个亚组；（1）纯合性CDKN2A/B缺失；（2）形态学（坏死和/或微血管增生）；（3）同时具备纯合性CDKN2A/B缺失和形态学4级标准的联合亚组。

结果

我们纳入了90例4级IDHm星形细胞瘤患者（本地队列，n = 35；TCGA队列，n = 55）。中位生存期为4.1年（95%CI 3.0 - 5.3）。当诊断基于纯合性CDKN2A/B缺失和世界卫生组织形态学4级标准时，生存期相当（5.2年对5.3年）。然而，在联合亚组中，生存期显著缩短（2.8年，p = 0.006）。