Expression of Dkk 1 in Endometrial Endometrioid Carcinoma & Its Correlation with Wnt / β-catenin Signaling Pathway

Abstract

Objective: Endometrial cancer is the most common form of cancer affecting female reproductive organs. Most common histologic type endometrioid carcinoma constitutes 75 to 80% of all cases. Studies on Dkk1 expression profiles and its inhibitory role in Wnt signaling pathway in genesis and development of endometrial carcinoma are very few. This study aims to investigate Dkk1 expression in endometrial carcinoma and its correlation with Wnt/β-catenin pathway. Methods: A total of 160 formalin fixed paraffin embedded samples including 50 cases each of endometrial atypical hyperplasia and endometrioid endometrial carcinoma along with 30 cases each of proliferative and secretory endometrium were included in this study. We investigated expression pattern of Dkk1, E-cadherin, β-catenin and c-myc in endometrial atypical hyperplasia and carcinoma as well as compared with that of proliferative and secretory endometrium. Immunohistochemistry and analysis were performed from July, 2018 to June, 2020. Results: We showed decreasing pattern of immunopositivity for Dkk1, E-cadherin and β-catenin from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Increasing c-myc immunopositivity was noted from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Moreover, decreasing Dkk1 immunopositivity was well correlated with both E-cadherin, β-catenin and c-myc immunopositivity. Conclusion: Decreasing Dkk1 positivity from benign endometrium to endometrioid carcinoma suggests a negative regulatory function of Dkk1 in endometrioid carcinoma. Dkk1 is downregulated in Wnt signaling pathway in endometrioid endometrial carcinoma. Thus, Dkk1 can show promise as a biomarker for screening endometrioid carcinoma. Future researches can study the reactivation of the Dkk1 gene that could be a valuable strategy for antagonizing Wnt signaling pathway.

Keywords: Endometrioid carcinoma, Dkk1, Wnt/β-catenin pathway, β-catenin, E-cadherin