Onishi Takafumi, Takashima Tsuyoshi, Kurashige Masako, Ohshima Kenji, Morii Eiichi
Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Medical Technology and Sciences, Faculty of Health Sciences, Kyoto Tachibana University, Kyoto, Japan; Research Center for Life and Health Sciences, Kyoto Tachibana University, Kyoto, Japan.
Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan; Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
Pathol Res Pract. 2022 Oct;238:154071. doi: 10.1016/j.prp.2022.154071. Epub 2022 Aug 12.
Enhancer of zeste homolog 2 (EZH2) epigenetically represses gene expression via trimethylation of lysine 27 on histone 3 (H3K27me3). Non-small cell carcinoma (NSCLC) has been reported to show high EZH2 and low H3K27me3 expression compared to normal lung tissues, but there are no studies examining the expression of EZH2 and H3K27me3 simultaneously with immunohistochemistry. In the present study, the expression of EZH2 and H3K27me3 was examined in surgically resected NSCLC. We enrolled 27 cases of squamous cell carcinoma (SCC), 73 cases of Lepidic, 77 of Papillary/Acinar, 51 of Solid, 31 of Micropapillary, and 12 of Mucinous subtypes of adenocarcinoma. First, we examined the expression of EZH2 and H3K27me3 in normal and metaplastic bronchial epithelium adjacent to NSCLC. Normal bronchial epithelium showed EZH2 expression in a limited number of basal cells and H3K27me3 expression in surface differentiated cells with cilia or mucus. In metaplastic bronchial epithelium, the number of EZH2-positive cells increased in multilayered basal cells, and H3K27me3-positive cells were observed in the superficial layer. Then, EZH2 and H3K27me3 expression was analyzed in NSCLC. Abundant EZH2 and rare H3K27me3 expression was detected in SCC, Papillary/Acinar, Solid and Micropapillary subtypes. In Mucinous subtype, EZH2 expression was hardly detected, and H3K27me3 expression was detected in almost all tumor cells. EZH2-expressing and H3K27me3-expressing tumor cells were similarly observed in Lepidic subtype, but double immunofluorescence revealed that EZH2 and H3K27me3 expression pattern was mutually exclusive. No co-expression of EZH2 and H3K27me3 was detected in all examined subtypes. To our knowledge, there have been no reports describing mutually exclusive expression pattern of EZH2 and H3K27me3.
zeste 同源物 2 增强子（EZH2）通过组蛋白 3 赖氨酸 27 位点的三甲基化（H3K27me3）在表观遗传上抑制基因表达。据报道，与正常肺组织相比，非小细胞癌（NSCLC）中 EZH2 表达高而 H3K27me3 表达低，但尚无研究通过免疫组织化学同时检测 EZH2 和 H3K27me3 的表达。在本研究中，对手术切除的 NSCLC 中 EZH2 和 H3K27me3 的表达进行了检测。我们纳入了 27 例鳞状细胞癌（SCC）、73 例鳞屑状、77 例乳头/腺泡状、51 例实体状、31 例微乳头状以及 12 例黏液性腺癌亚型。首先，我们检测了 NSCLC 邻近的正常和化生支气管上皮中 EZH2 和 H3K27me3 的表达。正常支气管上皮在少数基底细胞中显示 EZH2 表达，在有纤毛或黏液的表面分化细胞中显示 H3K27me3 表达。在化生支气管上皮中，多层基底细胞中 EZH2 阳性细胞数量增加，表层可见 H3K27me3 阳性细胞。然后，分析了 NSCLC 中 EZH2 和 H3K27me3 的表达。在 SCC、乳头/腺泡状、实体状和微乳头状亚型中检测到丰富的 EZH2 表达和罕见的 H3K27me3 表达。在黏液性腺癌亚型中，几乎未检测到 EZH2 表达，而在几乎所有肿瘤细胞中均检测到 H3K27me3 表达。在鳞屑状亚型中同样观察到表达 EZH2 和表达 H3K27me3 的肿瘤细胞，但双重免疫荧光显示 EZH2 和 H3K27me3 的表达模式相互排斥。在所有检测的亚型中均未检测到 EZH2 和 H3K27me3 的共表达。据我们所知，尚无报道描述 EZH2 和 H3K27me3 的相互排斥表达模式。
