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Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors
Brain Tumor Pathology ( IF 2.7 ) Pub Date : 2020-09-28 , DOI: 10.1007/s10014-020-00382-y
Keiichiro Kitahama 1 , Shohei Iijima 2 , Ayumi Sumiishi 1 , Akimasa Hayashi 1 , Kiyotaka Nagahama 1 , Kuniaki Saito 2 , Nobuyoshi Sasaki 2 , Keiichi Kobayashi 2 , Saki Shimizu 2 , Motoo Nagane 2 , Junji Shibahara 1
Affiliation  

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.



中文翻译:

弥漫性神经胶质瘤中H3K27me3水平降低:与1p / 19q编码相关,与恶性周围神经鞘瘤中H3K27me3丢失的差异有关

组氨酸H3在赖氨酸27(H3K27me3)的三甲基化作用是靶基因的转录阻遏物。近期的免疫组织化学研究报告称,弥漫性(特别是1p / 19q小码)神经胶质瘤中H3K27me3修饰的缺失。但是,我们没有使用常规免疫染色条件检测恶性周围神经鞘瘤(MPNSTs)中H3K27me3的丢失,观察到弥漫性胶质瘤中H3K27me3的丢失。因此,我们对手术切除的标本进行了免疫组织化学分析,以了解MPNSTs和弥漫性神经胶质瘤中H3K27me3状态的差异,并评估H3K27me3免疫组化的诊断价值。用标准的1:200稀释度的C36B11抗体染色显示,在11个MPNST中有5个中H3K27me3完全丧失,而大多数弥漫性神经胶质瘤(149/151,98。7%)显示弥漫性免疫反应性。在1:2000的抗体稀释度下,12.6%(19/151)的弥漫性神经胶质瘤显示H3K27me3缺失,这与1p / 19q编码显着相关(P  <0.001)。H3K27me3丢失预测IDH突变神经胶质瘤的1p / 19q编码缺失,其敏感性(56.2%)和特异性(100%)比ATRX保留或p53阴性结果高。总之,H3K27me3水平的降低与弥漫性神经胶质瘤的1p / 19q缺失有关。然而,减少的程度与MPNSTs不同,其结果取决于免疫染色条件。

更新日期:2020-09-28
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