Robust expression of EZH2 in endocervical neoplastic lesions

Abstract

The aim of this study was to evaluate the nuclear expression of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in endocervical neoplastic lesions such as invasive endocervical adenocarcinoma (ECA) and cervical in situ adenocarcinoma (AIS) in comparison with normal endocervix and non-neoplastic counterparts. A total of 54 consecutive neoplastic cases (37 ECA, 17 AIS) and 32 non-neoplastic endocervical lesions (15 reactive atypia, 9 microglandular hyperplasia, 3 tuboendometrioid metaplasia, 3 tunnel cluster, 2 endometriosis) were included in the study with adjacent normal endocervix if present. EZH2 immunoreactivity was evaluated semiquantitatively by three independent experts in lesions and adjacent normal glandular epithelium as well. EZH2 expression was defined robust if at least two of the three experts rated partial or diffuse positivity. Robust EZH2 expression was statistically compared among the neoplastic, non-neoplastic, and normal glandular epithelium samples. Diagnostic test capability of robust EZH2 expression was calculated. Fifty-three out of the 54 neoplastic cases (98%) showed robust EZH2 expression. Robust EZH2 expression was significantly less often (4 out of 32 cases, 12.5%) found in the non-neoplastic endocervical lesions ( p < 0.0001) and never (0 out of 66 samples) in the adjacent normal glandular epithelium. Robust EZH2 overexpression had a sensitivity and specificity of over 95% in detecting neoplastic lesions versus non-neoplastic lesions or normal glandular epithelium. EZH2 may play a role in the pathogenesis of endocervical neoplasia, and the detection of robust expression of EZH2 might be a useful differential diagnostic tool in problematic endocervical lesions in histology and cytology as well.

EZH2 and POU2F3 Can Aid in the Distinction of Thymic Carcinoma from Thymoma

“…Furthermore, the small number of cases available for rare thymic carcinoma subtypes limits our understanding of the sensitivity of immunohistochemical markers for these tumors. We also caution that EZH2 and POU2F3 are detectable in non-thymic carcinomas [ 12 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], and immunoreactivity for these markers does not imply thymic origin.…”

“…Applications of EZH2 IHC have also been explored for mesothelial [ 22 , 23 ], breast [ 24 ], prostate [ 25 ], biliary [ 26 ], endocervical [ 27 ], and liver [ 28 ] neoplasms, and therefore EZH2 may become a multi-purpose addition to a laboratory’s available immunostains. EZH2 staining of lymphocytes may be useful as an internal positive control but must be carefully distinguished from tumor cell staining.…”

Immune system‑associated genes increase malignant progression and can be used to predict clinical outcome in patients with hepatocellular carcinoma

“…EZH2 is expression is low in the normal liver, and is associated with methylation of histone H3K27 and recruitment of methyltransferases, which are involved in DNA replication for cancer progression, and stem cell maintenance and differentiation of other cell lineages, such as immune cells (32,33). Several studies have confirmed its prognostic value and importance in various types of cancer, including lymphoma, glioma, head and neck carcinoma, and cervical neoplasia (34)(35)(36)(37)(38). Novel therapeutic methods have been developed to target EZH2, although high expression of EZH2 is not always correlated with the malignancy of a cancer, such as in colorectal cancer (39)(40)(41).…”

Evaluation of Immunohistochemical Expression of Enhancer of Zeste Homolog 2 (EZH2) and Its Association With Clinicopathological Variables in Carcinoma Cervix

“…So far, various mechanisms have been postulated by which EZH2 is involved in cervical cancer progression. It is a histone methyltransferase and catalyzes methylation of histone H3 at lysine 27 (H3K27) leading to DNA methylation, chromatin remodeling, and silencing of tumor suppressor genes [8][9][10]. Thus, it plays an important role in pathophysiology of cancer and has become potential target for cancer therapy.…”

“…Enhancer of Zeste Homolog 2 (EZH2) is a histone methyltransferase and catalyses trimethylation of histone H3 at lysine 27 (H3K27) leading to DNA methylation, chromatin remodeling, and silencing of tumor suppressor genes [8][9][10]. It has oncogenic activity and is shown to inhibit cell differentiation and induces epithelial mesenchymal transition (EMT) directly via histone trimethylation.…”