Estrogen biosynthesis, phase I and phase II metabolism, and action in endometrial cancer

Endometrial cancer is the most common gynecological malignancy in the developed World. Based on their histopathology, clinical manifestation, and epidemiology, the majority of endometrial cancer cases can be divided into two groups: the more prevalent type 1 which is associated with unopposed estrogen exposure; and the less common type 2, which is usually not associated with hyper-estrogenic factors. This manuscript overviews the published data on the expression of genes encoding the estrogen biosynthetic enzymes, the phase I and phase II estrogen metabolic enzymes, and the estrogen receptors in endometrial cancer, at the mRNA, protein and enzyme activity levels. The potential role of altered expression of these enzymes and receptors in cancerous versus control endometrial tissue, and the implication of estrogens in tumor initiation and promotion, are discussed. Finally, based on the published data, a model of estrogen metabolism and actions is proposed for pre-cancerous and cancerous endometrial tissue, and the role of the estrogens in the progression of endometrial cancer from endometrial hyperplasia is suggested. (C) 2013 Elsevier Ireland Ltd. All rights reserved.