Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, Srinakharinwirot University, 114 Sukhumvit 23 Wattana, Bangkok, 10110, Thailand.
Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Henri-Dunant Road, Pathumwan, Bangkok, 10330, Thailand.
Sci Rep. 2022 Sep 5;12(1):15063. doi: 10.1038/s41598-022-19174-9.
Post-translational modification of histones is the crucial event that affect many tumor-specific traits. A diverse type of histone modifications had been reported in different cancers with prognostic implications. This study aimed to examine the degree of histone H3 modifications in salivary gland neoplasms and their associations with tumor pathologic characteristics and proliferative activity. The expression of H3K9Ac, H3K18Ac, H3K9Me3 and Ki-67 in 70 specimens of salivary gland neoplasms, consisting of 30 mucoepidermoid carcinoma (MEC), 20 adenoid cystic carcinoma (ACC) and 20 pleomorphic adenoma (PA), were investigated immunohistochemically. The immunohistochemical scoring of 3 histone modification types and Ki-67 labeling index were determined. Overall, MEC demonstrated elevated H3K9Ac level compared with benign PA. Increased H3K9Me3 in MEC was positively correlated with small nest invasion at tumor front, advanced pathologic grade, and elevated proliferative index. In addition, the significant upregulation of all 3 types of histone H3 modification was noted in solid subtype of ACC and associated with increased cell proliferation. This study indicates that salivary gland neoplasms differentially acquire distinct patterns of histone H3 modification, which impact prognostically relevant cancer phenotypes. The hyperacetylation and methylation of histone H3 could be underpinning the prognostically worsen solid type of ACC, and the trimethylation of H3K9 may be involved in aggressive characteristics of MEC.
组蛋白的翻译后修饰是影响许多肿瘤特异性特征的关键事件。不同类型的组蛋白修饰已在不同癌症中被报道，并具有预后意义。本研究旨在研究唾液腺癌中组蛋白 H3 修饰的程度及其与肿瘤病理特征和增殖活性的关系。用免疫组织化学方法检测了 70 例唾液腺癌标本（包括 30 例黏液表皮样癌（MEC）、20 例腺样囊性癌（ACC）和 20 例多形性腺瘤（PA））中 H3K9Ac、H3K18Ac、H3K9Me3 和 Ki-67 的表达。确定了 3 种组蛋白修饰类型和 Ki-67 标记指数的免疫组织化学评分。总的来说，MEC 与良性 PA 相比，H3K9Ac 水平升高。MEC 中 H3K9Me3 的增加与肿瘤前缘的小巢浸润、高级别病理分级和增殖指数升高呈正相关。此外，在 ACC 的实性亚型中观察到所有 3 种组蛋白 H3 修饰类型的显著上调，并与细胞增殖增加有关。本研究表明，唾液腺癌获得了不同的组蛋白 H3 修饰模式，这些模式影响与预后相关的癌症表型。组蛋白 H3 的乙酰化和甲基化增加可能是 ACC 实性亚型预后恶化的基础，H3K9 的三甲基化可能参与了 MEC 的侵袭性特征。
