目的:明确K27M-H3.3型突变对H3K27me3蛋白表达的影响,探讨丘脑多级别胶质瘤H3F3A基因 K27M-H3.3型突变与患者的预后相关性.方法:整理并分析2013年1月至2016年12月经术后病理证实的24例丘脑胶质瘤的临床资料,包括性别、年龄、发病年龄、病程、首发症状、临床表现、影像学资料、病理分型等,记录各病例总生存期及无进展生存期.将患者分为实验组(K27M-H3.3型突变阳性)及对照组(K27M-H3.3型突变阴性).采用H3K27me3抗体免疫组织化学后复染,观察 H3K27me3蛋白在肿瘤组织中的表达情况并摄片.采用Kaplan-Meier统计方法分析两组患者预后差异性.结果:11例K27M-H3.3型突变阳性患者肿瘤组织切片均表现出明显的H3K27me3染色细胞减少及大片染色缺失区域.其中少部分切片在染色缺失区域中呈现局部零星环状及带状染色阳性,为血管内皮细胞及成纤维细胞染色,并非肿瘤细胞.突变阴性者H3K27me3核染色极其显著,未见染色细胞减少及染色缺失区域.Kaplan-Meier分析、log-rank检验提示实验组与对照组总生存期和无进展生存期差异无统计学意义(分别为P=0.335与P=0.097).结论:K27M-H3.3型突变可明显抑制 H3组蛋白第27位氨基酸三甲基化,造成H3K27me3蛋白表达减少,H3F3A基因H3.3K27M突变与预后关系有待进一步研究.%Objective: To investigate the relationship between H3.3K27M mutation and H3K27me3 protein expression by immunohistochemistry (IHC) and to discuss the correlation between K27M-H3.3 mutation and thalamic glioma prognosis. Methods: We Collected the clinical documents and data of 24 thalamic glioma patients who received surgical resection from January 2013 to December 2016, including sex, age, initial symptoms, clinical manifestations, CT/MRI images and pathologic test results. We recorded each patient's surviving data, including progress-free survival (PFS) and overall survival (OS). Finally, we separated them into experimental group and control group. The sections were tested by IHC with H3K27me3 antibody in order to estimate H3K27me3 protein expression. Analysis of prognosis was investigated by the SPSS V20.0 software. Results: The levels of H3K27 trimethylation (H3K27me3) were reduced globally in all the 11 H3.3K27M patient sample sections, while all the control group sections presented normally, lack of reduced or even deleted H3K27me3 areas. There was no significant statistical difference in OS and PFS between these two groups. Conclusion: The K27M-H3.3 mutation can severely lead to H3K27me3 reduction or even deletion, due to the reduced trimethylation of the 27th amino of H3 histone by H3.3K27M mutation. The prognostic factor of K27M-H3.3 mutation is still unclear.
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