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

Abstract

Carcinoma cervix is the fourth most common cancer worldwide and is one of the leading causes of cancer death in women. Recently, immunohistochemical expression of biomarkers has been utilized as indicators of disease progression, aggressiveness for predicting the prognosis in various cancers. DNA methylation of genes plays an important role in pathogenesis of carcinoma cervix and detection of aberrant methylation can be utilized for detection of carcinoma cervix and monitoring of its progression. Enhancer of Zeste Homolog 2 (EZH2) is a histone methyltransferase and catalyzes methylation of histone H3 and plays an important role in tumor cell proliferation, invasion, and metastasis. The aim of this study was to analyze the pattern, distribution, and grade of immunohistochemical expression of EZH2 in carcinoma cervix and study its association with clinico-pathological variables such as age, site and size of tumor, type of growth, tumor grade, histological subtype, lymph node metastasis, and stage of the tumor according to the Federation of Gynaecology and Obstetrics (FIGO). This observational study was carried out in the Department of Pathology & Lab Medicine, at our institute. A total of 60 consecutive histopathologically confirmed cases of carcinoma cervix from January 2018 to June 2022 were subjected to immunohistochemistry (IHC) for EZH2. The immunohistochemical score for each case was obtained by multiplying the intensity and percentage of positive cells for EZH2. An immunohistochemical score of four or greater than four was considered as high immunoexpression. The immunohistochemical results were correlated with clinico-pathological variables. The data were analyzed using relevant statistical methods using SPSS version 23 (IBM Corp., Armonk, NY). To find the significant difference (p value) and association, chi-square test along with Pearson chi-square were used, wherever necessary. A p value of <0.05 was considered as significant. High immunoexpreesion of EZH2 exhibited a significant association (p < 0.05) with the tumor grade, histologic subtype, lymphnode metastasis, and FIGO stage. The results of our study affirm that a significant association exists between immunohistochemical expression of EZH2 with tumor grade, histological subtype, lymphnode metastasis, and FIGO stage which can be utilized in future studies with larger sample size to further strengthen the association of EZH2 immunoexpression in cancer cervix patients that may aid in the development of the targeted therapy in near future.