Abstract 945: The identification of subgroups of obese women with differing endometrial/systemic estrogenic metabolism: Potential consequences in the development of endometrial cancer
Authors: Alejandra Villavicencio, Elizabeth Medina, Yenny Muñoz, Paulina Peñaloza, Fancy Gaete, Francisco Castro, Catalina Albornoz, Miguel Celis, Macarena Vargas, Gareth Owen
Journal: Cancer Research (2012)

Abstract Background: Enhanced endometrial proliferation correlates obesity to type-I (estrogen-dependent) endometrial cancer (EC). However, not all obese women develop type-I EC. Our laboratory identified cycling obese women without type-I EC with differing endometrial proliferation levels: Obese High Proliferating (OHP) and Obese Low Proliferating (OLP). We propose that these differences are the result of impaired endometrial/systemic estrogenic metabolism. Objectives: To assess the endometrial activity and/or expression of estrogen metabolic enzymes, such as aromatase and sulfatase, and the endometrial/systemic level of 17β-estradiol (E2), estrone (E1), estrone sulfate (E1-S) in those subgroups of obese patients. Methodology: The endometrial tissue and blood samples were obtained from pre-menopausal women in the proliferative phase (without type-I EC) with body mass index (BMI) = 18-24.9 Kg/m2 (normal-weight, N, n=10), BMIβ 30 kg/m2 (obese, OHP, n=14; OLP, n=6) and from obese women with type-I EC (n=12). Endometrial aromatase activity was assessed by measuring the amount of 3H2O released from tritiated androstenedione (substrate), and aromatase expression was measured by immunohistochemistry. Sulfatase activity was assayed using [3H] E1-S (substrate) and the [3H] product was determined by liquid scintillation. Endometrial and serum E2, E1, E1-S levels were determined by radioimmunoassay. Results: OHP demonstrated increased endometrial activity (26%, P&amp;lt;0.05) and expression (71.8%, P&amp;lt;0.05) of aromatase, higher endometrial E2 (25%, P&amp;lt;0.05) and E1-S (20%, P&amp;lt;0.05) levels, increased circulating E2 (57.1%, P&amp;lt;0.05) and E1-S (42.6%, P&amp;lt;0.05) levels compared with OLP group. In addition, OHP did not differ from OLP in endometrial sulfatase activity and endometrial/circulating E1 levels. No differences were observed between OLP and normal-weight groups in relation to aromatase activity/expression, circulating levels of E2, E1, E1-S, and endometrial levels of E2. Interestingly, obese women with type-I EC possessed similar aromatase and sulfatase activity as OHP. Conclusions: These data suggest that the E2 produced in the endometrial tissue from OHP group could amplify the estrogenic action of estrogens delivered via the circulation and explain the higher endometrial proliferation observed in this group. Our data may help identify obese women more susceptible to develop type-I EC, allowing early intervention and a potential reduction in mortality. (FONDECYT 1110232). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 945. doi:1538-7445.AM2012-945