Wnt/β-catenin Signaling in Endometrioid Endometrial Cancer and Precursor Lesions

Abstract

Endometrioid endometrial carcinoma (EEC) is most common invasive malignancy of female genital tract. In spite of advances in diagnosis and treatment, incidence of EEC has been rising because of increasing aging population and prevalence of obesity. Therefore, there is need of research exploring the underlying molecular mechanism of EEC and its precursors. Wnt/ β-catenin signaling are involved in the progression and invasion of EEC. However, the potential role of Wnt/ β-catenin signaling and its effectors in endometrial cancer and precursor lesions remains to be investigated. In the present study a total of 95 samples of endometrial biopsies were assessed histopathologically along with β-catenin expression by immunohistochemistry and promoter methylation of adenomatous polyposis coli (APC) gene by bisulfite method. Women age ranged from 35 to 70 years whose endometrial biopsy and resected samples were obtained. Expression of β-catenin was observed in 28/39; 72% of EEC, 23/37; 62% of precancer cases and 4/19; 21% of normal proliferative endometrium. APC promoter was completely unmethylated in all controls (14/14) and precancer (10/10) groups, however, only one case (1/13, 8%) of cancer was methylated. The present study showed that expression of β-catenin was upregulated in EEC and precursor lesions suggesting involvement of Wnt/ β-catenin signaling from an early stage of development of cancer from precancer. The information might offer a potential therapeutic target for EEC and could also be used as a screening tool in endometrial hyperplasia (EH) cases for detecting potentially precancerous lesions.