Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas
Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas
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DOI：
10.1007/s10014-020-00369-9
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发表时间：
2020-06-11
影响因子：
3.3
通讯作者：
Yamaguchi, Shigeru
中科院分区：
文献类型：
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作者：
Ishi, Yukitomo;Takamiya, Soichiro;Yamaguchi, Shigeru
本研究旨在探讨脊髓胶质瘤中H3 F3 A K27 M突变（H3 K27 M）的临床意义，并分析H3 K27 M、H3 K27 me 3状态与EZH 2表达及预后的关系。对脊髓弥漫性胶质瘤患者进行H3 F3 A、HIST 1H 3B、TERT启动子、IDH 1/2和BRAF基因分析，而不考虑世界卫生组织（WHO）分级。通过免疫组化分析H3 K27 me 3状态和EZH 2表达。此后，使用对数秩检验回顾性分析H3 K27 M、H3 K27 me 3状态和EZH 2表达与预后之间的关联。共分析了26例病例，其中WHO 4级5例，3级9例，2级12例。虽然WHO 2级病例倾向于呈现有利的总生存率，但差异无统计学显著性。H3 K27 M在4例4级病例（80%）和3例3级病例（33%）中检出，与3级和4级病例的预后无关。在WHO 2-4级病例中，保留的H3 K27 me 3和阴性EZH 2表达的组合与有利的总生存期相关（p = 0.03）。H3 K27 me 3状态和EZH 2表达的组合被认为是WHO 2-4级弥漫性脊髓胶质瘤的潜在预后标志物。
The objective of this study is to clarify clinical significance of theH3F3A K27Mmutation (H3K27M) and analyze the correlation between H3K27M, H3K27me3 status, and EZH2 expression and prognosis in spinal cord gliomas. Patients with spinal cord diffuse glioma regardless of World Health Organization (WHO) grade underwent genetic analysis forH3F3A, HIST1H3B,TERTpromoter,IDH1/2, andBRAF. H3K27me3 status and EZH2 expression were analyzed through immunohistochemistry. Thereafter, the association between H3K27M, H3K27me3 status, and EZH2 expression and prognosis was retrospectively analyzed using the log-rank test. A total of 26 cases, 5 with WHO grade 4, 9 with grade 3, and 12 with grade 2 glioma, were analyzed. Although WHO grade 2 cases tended to present favorable overall survival, the difference was not statistically significant. H3K27M, which was detected in four grade 4 cases (80%) and three grade 3 cases (33%), was not associated with prognosis among grade 3 and 4 cases. Among WHO grade 2-4 cases, the combination of retained H3K27me3 and negative EZH2 expression was correlated with favorable overall survival (p = 0.03). The combination of H3K27me3 status and EZH2 expression was considered as a potential prognostic marker in WHO grade 2-4 diffuse spinal cord gliomas.