LAUSR

Simple Summary Endometrioid endometrial cancer is typically estrogen-positive and associated with obesity. Indeed, circulating estrogens are strongly and linearly related to adiposity and increased BMI, which have been identified as the most important risk factors for endometrioid endometrial cancer. However, the relationship between excess body weight and endometrial cancer is more complex, and, besides the unopposed estrogens, involves multiple mechanisms, including hyperinsulinemia, altered adipokines, inflammation, and oxidative stress associated with obesity. We investigated the association between classical tumor prognostic factors (i.e., tumor size (T), and nodal (N) and metastatic (M) status) and the levels of leptin, proinflammatory cytokines, and oxidative stress, together with BMI, among type I (endometrioid) and type II endometrial cancer patients. We found that BMI, leptin, IL-6, and reactive oxygen species correlated with T, N, and M status in type I, but not in type II endometrial cancers. This could open new therapeutic perspectives based on the specific pathogenetic mechanisms involved. Abstract Endometrioid endometrial cancer is associated with increased BMI and obesity through multiple pathogenetic mechanisms involving hyperestrogenism, hyperinsulinemia, altered adipokine secretion, inflammation, and oxidative stress. In the present study, we aimed to investigate the correlation between BMI, leptin, the proinflammatory cytokines IL-6 and TNFα, reactive oxygen species (ROS), and the traditional prognostic factors T, G, N and M status among type I endometrioid and type II endometrial cancer patients. We enrolled 305 consecutive endometrial cancer patients prospectively. We found that BMI, leptin, and IL-6 significantly correlated with T status, N status, and M status among endometrioid type I endometrial cancer patients. Among type II endometrial cancer patients, BMI and leptin did not correlate with any of the prognostic parameters, whereas there was a positive correlation between IL-6 and the presence of distant metastases. In the multivariate regression analysis, BMI, leptin, and IL-6 were independent predictive variables of T, N, and M status in endometrioid type I endometrial cancer patients. Our study demonstrates that weight gain, adiposity-related adipokines, inflammation, and oxidative stress correlate with the prognostic factors of endometrioid endometrial cancer. Knowledge of the role of obesity-related biological pathways and mediators in the pathogenesis and prognosis of endometrioid endometrial malignancies may offer new perspectives on combined therapeutic strategies that have not been explored to date, both in the advanced disease and in the adjuvant setting.