Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors
Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors
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DOI：
10.1007/s10014-020-00382-y
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发表时间：
2020-09-28
影响因子：
3.3
通讯作者：
Shibahara, Junji
中科院分区：
文献类型：
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作者：
Kitahama, Keiichiro;Iijima, Shohei;Shibahara, Junji
组蛋白H3在赖氨酸27位的三甲基化(H3K27me3)是靶基因的转录抑制因子。最近的免疫组织化学研究报告了弥漫性(尤其是1p/19q缺失)胶质瘤中H3K27me3修饰的缺失。然而，我们没有观察到H3K27me3在弥漫性胶质瘤中的丢失，在恶性周围神经鞘瘤(MPNSTs)中使用常规免疫染色条件检测H3K27me3丢失。因此，我们对手术切除的标本进行免疫组织化学分析，以了解H3K27me3在MPNSTs和弥漫性胶质瘤中状态的差异，并评价H3K27me3免疫组织化学在诊断中的价值。用1：200稀释度的C36B11抗体染色，11例MPNST中有5例H3K27me3完全消失，而大多数弥漫性胶质瘤(149/151，98.7%)呈弥漫性免疫反应。在抗体稀释倍数为1：2000时，12.6%的弥漫性胶质瘤出现H3K27me3缺失，与1p/19q共缺失显著相关(P<；0.001)。在IDH突变的胶质瘤中，H3K27me3缺失预测1p/19q共缺失，其敏感性(56.2%)和特异性(100%)低于ATRX滞留或P53阴性结果。综上所述，弥漫性胶质瘤中H3K27me3水平的降低与1p/19q共缺失相关；然而，其降低的程度与MPNSTs不同，结果取决于免疫染色条件。
Trimethylation of histone H3 at lysine 27 (H3K27me3) acts as a transcriptional repressor of target genes. Recent immunohistochemical studies have reported a loss of H3K27me3 modification in diffuse (especially 1p/19q-codeleted) gliomas. However, we did not observe H3K27me3 loss in diffuse gliomas using routine immunostaining conditions for the detection of H3K27me3 loss in malignant peripheral nerve sheath tumors (MPNSTs). Therefore, we conducted immunohistochemical analysis of surgically resected specimens to understand the differences in the H3K27me3 status in MPNSTs and diffuse gliomas and evaluate the diagnostic utility of H3K27me3 immunohistochemistry. Staining with a standard 1:200 dilution of the C36B11 antibody showed a complete loss of H3K27me3 in 5 out of 11 MPNSTs, whereas most diffuse gliomas (149/151, 98.7%) showed diffuse immunoreactivity. At a 1:2000 antibody dilution, 12.6% (19/151) of the diffuse gliomas showed H3K27me3 loss, which was significantly associated with 1p/19q codeletion (P < 0.001). H3K27me3 loss predicted 1p/19q codeletion in IDH-mutant gliomas with lower sensitivity (56.2%) and higher specificity (100%) than ATRX retention or p53 negative result. In conclusion, reduction in H3K27me3 levels was associated with 1p/19q codeletion in diffuse gliomas; however, the extent of reduction differed from that in MPNSTs, and the results depended on the immunostaining conditions.