Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p۱۴ and p۱۶ in Iranian Endometrial Carcinoma Patients

Background: Endometrial cancer is a common gynecological malignancy with good prognosis in the early stages of the disease. The CpG island in the promoter region of tumor-suppressor genes are frequently methylated in various types of human cancers. In the present study, we have examined the methylation status of the p۱۶INK۴a and p۱۴ARF genes in endometrial cancer and healthy endometrium with the aim to identify correlations between promoter hypermethylation, disease risk, and clinicopathological parameters.Methods: We collected ۲۸ formalin fixed paraffin embedded samples and ۲۶ blood samples from endometrial cancer patients and ۲۲ controls. Methylation-specific PCR was applied to analyze the promoter methylation status of the p۱۶INK۴a and p۱۴ARF genes in the studied population. The results were analyzed with SPSS software version ۲۰.Results: There was a significant difference between the study groups and the presence of promoter CpG hypermethylation status in the p۱۴ (P<۰.۰۰۰۱) and p۱۶ (P<۰.۰۵) genes. p۱۴ hypermethylation in the blood samples was associated with depth of myometrial invasion in endometrial cancer (P=۰.۰۳). A significant association existed between p۱۶methylation in tissue with endometrial cancer grade (P=۰.۰۶). No statistically significant difference existed between the p۱۶INK۴a and p۱۴ARF promoter hypermethylations in blood (P=۰.۱۷۷) and formalin fixed paraffin embedded (P=۰.۲۲۱) samples. An association existed between p۱۶INK۴a and p۱۴ARF gene hypermethylations in blood and tissue with diabetes.Conclusion: Our results have confirmed that epigenetic mechanisms play an important role in endometrial cancer incidence. They can be utilized as prognostic biomarkers for endometrial cancer. The lack of a significant difference between the p۱۶INK۴a and p۱۴ARF promoter hypermethylations in blood and formalin fixed paraffin embedded samples has indicated that methylation status of a blood sample can be an early, non-invasive diagnostic marker in endometrial cancer.