The identification of two subgroups of obese women with differing endometrial proliferation levels: potential consequences in the development of endometrial cancer

Abstract

Enhanced endometrial proliferation correlates obesity to type-I (estrogen-dependent) endometrial cancer (EC). Our aim was to distinguish obese women (without EC) with differing endometrial proliferation. Endometrial and blood samples were obtained from normal-weight and obese women without EC. Type-I EC samples were obtained from obese patients. On measuring endometrial proliferation (Ki67 and phosphorylated histone H3 (p-H3)), two groups of obese women without EC were identified: obese(High Proliferating) (O-HP) and obese(Low Proliferating) (O-LP). Increased Ki67 (88.5%, P<0.001), p-H3 (62.6%, P<0.01), 17 beta-estradiol/progesterone ratio (46.3%, P<0.01) and endometrial estrogen receptor alpha (ER alpha) (82.2%, P<0.001) were observed in O-HP compared with O-LP patients. ECs possessed similar ER alpha and enhanced proliferation as O-HP, suggesting that O-HP women are at higher risk of type-I EC. O-LP women were indistinguishable from normal-weight women regarding these determinants of endometrial proliferation, ER alpha and 17 beta-estradiol/progesterone ratio. Our data may further define the obesity phenotype in regards to type-I EC risk and may help identify obese women more susceptible to develop type-I EC, allowing early intervention and a potential reduction in mortality.