The present study immunohistochemically investigated trimethylation of lysine 27 of histone 3 (H3K27me3) expression in 769 endometrial carcinomas and 196 uterine mesenchymal tumors. One dedifferentiated endometrial carcinoma (DEC) and one carcinosarcoma showed H3K27me3 deficiency that was limited to undifferentiated and sarcomatous components, respectively. Switch/sucrose nonfermenting (SWI/SNF) complex subunits (SMARCA4, SMARCB1, and ARID1A/1B) and mismatch repair proteins were proficient in both tumors. The dimethylation of H3K27 (H3K27me2) was deficient in the undifferentiated component, whereas the sarcomatous component had scattered H3K27me2-positive cells. CXorf67, which inhibits PRC2 function, was diffusely expressed in the sarcomatous component. CXorf67 was negative in the undifferentiated component, which was submitted to a genetic analysis and showed no alterations in PRC2 core subunits or H3K27. The present results suggest H3K27 methylation dysregulation as a cause of SWI/SNF-proficient DEC and carcinosarcoma and imply differences in their level of and the mechanisms underlying H3K27 methylation dysregulation.

本研究通过免疫组织化学方法研究了 769 例子宫内膜癌和 196 例子宫间质肿瘤中组蛋白 3 (H3K27me3) 赖氨酸 27 表达的三甲基化。一种去分化子宫内膜癌 (DEC) 和一种癌肉瘤显示 H3K27me3 缺陷，分别仅限于未分化和肉瘤成分。开关/蔗糖非发酵 (SWI/SNF) 复合体亚基（SMARCA4、SMARCB1 和 ARID1A/1B）和错配修复蛋白在两种肿瘤中均具有丰富的作用。 H3K27 (H3K27me2) 的二甲基化在未分化成分中存在缺陷，而肉瘤成分则有分散的 H3K27me2 阳性细胞。抑制 PRC2 功能的 CXorf67 在肉瘤成分中广泛表达。 CXorf67 在未分化成分中呈阴性，经遗传分析显示 PRC2 核心亚基或 H3K27 没有变化。目前的结果表明，H3K27 甲基化失调是 SWI/SNF 熟练的 DEC 和癌肉瘤的一个原因，并且意味着 H3K27 甲基化失调的水平和机制存在差异。