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Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas.
Brain Tumor Pathology ( IF 2.7 ) Pub Date : 2020-06-11 , DOI: 10.1007/s10014-020-00369-9
Yukitomo Ishi 1 , Soichiro Takamiya 1 , Toshitaka Seki 1 , Kazuyoshi Yamazaki 1 , Kazutoshi Hida 2 , Kanako C Hatanaka 3 , Yusuke Ishida 4 , Yoshitaka Oda 4 , Shinya Tanaka 4 , Shigeru Yamaguchi 1
Affiliation  

The objective of this study is to clarify clinical significance of the H3F3A K27M mutation (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 for H3F3A, HIST1H3B, TERT promoter, IDH1/2, and BRAF. 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.

中文翻译:

H3K27M 突变、组蛋白 H3K27 甲基化状态和 EZH2 表达在弥漫性脊髓胶质瘤中的预后作用。

本研究的目的是阐明H3F3A K27M突变 (H3K27M) 的临床意义,并分析 H3K27M、H3K27me3 状态和 EZH2 表达与脊髓胶质瘤预后的相关性。无论世界卫生组织 (WHO) 分级如何,脊髓弥漫性胶质瘤患者都接受了H3F3A、HIST1H3BTERT启动子、IDH1/2BRAF 的遗传分析. 通过免疫组织化学分析 H3K27me3 状态和 EZH2 表达。此后,使用对数秩检验回顾性分析 H3K27M、H3K27me3 状态和 EZH2 表达和预后之间的关联。共分析了 26 例病例,其中 5 例为 WHO 4 级,9 例为 3 级,12 例为 2 级胶质瘤。尽管 WHO 2 级病例倾向于呈现良好的总生存率,但差异无统计学意义。H3K27M 在 4 个 4 级病例(80%)和 3 个 3 级病例(33%)中检测到,与 3 级和 4 级病例的预后无关。在 WHO 2-4 级病例中,保留的 H3K27me3 和阴性 EZH2 表达的组合与良好的总生存期相关(p = 0.03)。H3K27me3 状态和 EZH2 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。
更新日期:2020-06-11
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