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.
Highlights
Endocervical adenocarcinoma (ECA) is the second most common histological type of cervical cancer; it comprises approximately 20 to 25% of cervical malignancies [1] and has a poorer prognosis than squamous cell carcinoma [2]
It is well established that the pRB pathway is involved in the pathogenesis of cervical cancer due to the interaction with HR-HPV E7 oncoproteins leading to genomic instability [4]
We examined Enhancer of zeste homolog 2 (EZH2) expression in ECA and AIS, compared with non-neoplastic cervical lesions and normal glandular epithelium
Summary
Endocervical adenocarcinoma (ECA) is the second most common histological type of cervical cancer; it comprises approximately 20 to 25% of cervical malignancies [1] and has a poorer prognosis than squamous cell carcinoma [2]. Cervical adenocarcinomas and their precursor lesions are heterogeneous and have several different subtypes, most of them closely related to HR-HPVs [3]. It is known that viral E6/E7 oncoproteins may interact with different types of epigenetic enzymes, such as p300, CBP, and pCAF, which can be involved in the oncogenesis [5]. In conjunction with the p53 protein, it induces tumor cell proliferation, metastasis, and immortalization [6]
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