Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok, 10400, Thailand.
Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, 10400, Thailand.
Head Neck Pathol. 2021 Jun;15(2):408-415. doi: 10.1007/s12105-020-01209-0. Epub 2020 Jul 27.
Enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 that catalyzes trimethylation of H3K27 (H3K27me3), has been shown to promote tumor development and progression. Expression of EZH2 is associated with cell cycle regulation and cell proliferation in various neoplasms. Oral verrucous hyperplasia (OVH) and Oral verrucous carcinoma (OVC) are rare entities and share several clinical and histopathologic features. Problems distinguishing these lesions are added by a lack of adjacent normal tissue of the biopsy samples and poorly oriented tissue sections. The aim of this study was to investigate the expression of EZH2 and H3K27me3 in OVH and OVC and comparing the expression with normal oral mucosa and oral squamous cell carcinoma (OSCC). Seventy-eight samples, including 25 cases of OVC, 8 cases of OVH, 35 cases of OSCC and 10 cases of normal oral mucosa, were retrieved and submitted for immunohistochemical staining. The results demonstrated that the mean labeling indices (LIs) of EZH2 and H3K27me3 expression were highest in OSCC, followed by the OVC, OVH, and normal mucosa. Statistical differences in EZH2 LI were observed among these lesions whereas H3K27me3 LI was significantly different among OSCC, OVH and normal mucosa. EZH2 LI was found to have a sensitivity of 72.00% and specificity of 87.50% in distinguishing OVH from OVC, and a sensitivity of 57.14% and specificity of 84.00% in distinguishing OVC from OSCC. A positive correlation between EZH2 and H3K27me3 expression was significantly found in OVC but not in OVH and OSCC. These findings highlight the involvement of epigenetic regulation by EZH2-mediated H3K27me3 in the pathogenesis of OVH and OVC, and EZH2 expression indicates disease progression of these verrucous lesions. Diagnostic test analysis further suggests that EZH2 may be used as an additional test for differentiating OVH from OVC in questionable cases.
增强子结合锌指蛋白 2（EZH2）是多梳抑制复合物 2 的一个组成部分，可催化 H3K27 的三甲基化（H3K27me3），已被证明可促进肿瘤的发展和进展。EZH2 的表达与各种肿瘤中的细胞周期调节和细胞增殖有关。口腔疣状增生（OVH）和口腔疣状癌（OVC）是罕见的实体，具有许多临床和组织病理学特征。由于活检样本缺乏相邻的正常组织和组织切片方向不佳，使得区分这些病变的问题更加复杂。本研究旨在研究 EZH2 和 H3K27me3 在 OVH 和 OVC 中的表达，并将其与正常口腔黏膜和口腔鳞状细胞癌（OSCC）进行比较。共检索了 78 例标本，包括 25 例 OVC、8 例 OVH、35 例 OSCC 和 10 例正常口腔黏膜，进行免疫组织化学染色。结果表明，EZH2 和 H3K27me3 表达的平均标记指数（LI）在 OSCC 中最高，其次是 OVC、OVH 和正常黏膜。这些病变中 EZH2 LI 存在统计学差异，而 H3K27me3 LI 在 OSCC、OVH 和正常黏膜之间存在显著差异。EZH2 LI 在区分 OVH 与 OVC 时具有 72.00%的敏感性和 87.50%的特异性，在区分 OVC 与 OSCC 时具有 57.14%的敏感性和 84.00%的特异性。在 OVC 中发现 EZH2 和 H3K27me3 表达之间存在显著的正相关，但在 OVH 和 OSCC 中没有发现。这些发现强调了 EZH2 介导的 H3K27me3 对 OVH 和 OVC 发病机制的表观遗传调控作用，EZH2 表达表明这些疣状病变的疾病进展。诊断测试分析进一步表明，EZH2 可作为区分可疑病例中 OVH 与 OVC 的附加测试。
