Evaluation of expressions of DNMT-2 and hdac 4 genes which are role in epigenetic modification of carcinogenesis steps of endometrial carcinoma

Objective: To evaluate the expression of DNMT-2 and HDAC4 genes involved in epigenetic modification of carcinogenesis steps of endometrial carcinoma. Material and Methods: The cases of the endometrial biopsy materials in the paraffin block between 2009-2019 were selected from the archives of the Medical Pathology Department of Karadeniz Tecnhnical University Faculty of Medicine. The cases were classified as proliferative endometrium, hyperplasia without atypia, endometrial intraepithelital neoplasia and endometrial carcinoma (grade 1-2-3) having 18 cases in each group. The demographic characteristics of the cases that have been selected from the archive screening, such as age, gravida, comorbidity, smoking history, and tumor grades of endometrial biopsies were determined and recorded from computer records and pathology request forms. Hematoxylin & Eosin stained preparations of the cases were re-evaluated and suitable blocks representing the tumor were selected for immunohistochemical examination. IBM SPSS Statistics 22 was used for statistical analysis. For comparison between groups, parametric One-Way ANOVA test was used in groups with normal distribution, non-parametric Mann-Whitney U Test and Bonferoni corrected Kruskal-Wallis Test were used in groups that did not show normal distribution. H score was used when evaluating DNMT2 and HDAC4. P value of 0.05 and below was considered to be statistically significant. Results: Considering the average age of the groups, it was found statistically significant that endometrial cancer was seen in advanced age (p = 0.00). The difference between the groups in terms of DNMT 2 stromal expression was considered statistically significant (p = 0.00). In terms of DNMT 2 stromal expression, a statistically significant difference was found between endometrial carcinoma, endometrial intraepithelial neoplasia and endometrial hyperplasia without atypia and proliferative endometrium (p <0.05). In terms of DNMT 2 glandular expression, an increase was observed among the groups towards endometrial carcinoma, and this increase was considered statistically significant (p = 0.00). A statistically significant difference was found between endometrial carcinoma, endometrial intraepithelial neoplasia and endometrial hyperplasia without atypia and proliferative endometrium groups (p <0.05). The difference between the groups in terms of HDAC 4 stromal expression was considered statistically significant (p = 0.00). A statistically significant difference was found between endometrial carcinoma and endometrial intraepithelial neoplasia and proliferative endometrium (p <0.05). In terms of HDAC4 glandular expression, a decrease towards endometrial carcinoma was observed among the groups. This decrease was considered statistically significant (p = 0.00). In terms of HDAC 4 stromal expression, a statistically significant difference was found between endometrial carcinoma and endometrial intraepithelial neoplasia and proliferative endometrium groups (p <0.05). Conclusion: It was observed that DNMT 2 and HDAC 4 could be a guide in distinguishing endometrial cancer from precancerous lesions. Being a good biomarker for clinicians to determine diagnosis and treatment; it will enable them to be used in many different types of cancers for the future. According to the results of our study, it was thought that if a more detailed investigation of histone-mediated epigenetic changes in endometrial carcinoma was conducted, it would be possible to better understand the neoplastic process and to develop new targeted therapies.