Mutually exclusive expression of EZH2 and H3K27me3 in non-small cell lung carcinoma

Takafumi Onishi; Tsuyoshi Takashima; Masako Kurashige; Kenji Ohshima; Eiichi Morii

doi:10.1016/j.prp.2022.154071

Mutually exclusive expression of EZH2 and H3K27me3 in non-small cell lung carcinoma

Pathol Res Pract. 2022 Oct:238:154071. doi: 10.1016/j.prp.2022.154071. Epub 2022 Aug 12.

Authors

Takafumi Onishi¹, Tsuyoshi Takashima², Masako Kurashige², Kenji Ohshima³, Eiichi Morii⁴

Affiliations

¹ 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.
² Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan; Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
³ Division of Cancer Biology, Signalling and Cancer Metabolism Team, The Institute of Cancer Research, London, UK.
⁴ Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan; Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan. Electronic address: morii@molpath.med.osaka-u.ac.jp.

PMID: 35985089
DOI: 10.1016/j.prp.2022.154071

Abstract

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.

Keywords: EZH2; Epigenetics; H3K27me3; Lung cancer; Metaplasia; Non-small cell lung carcinoma.