Endometrial cancer chemoprevention: implications of diverse pathways of carcinogenesis

Endometrial cancers may be divided into two groups, reflecting differences in clinical behavior and pathogenesis. Endometrioid adenocarcinoma, which accounts for the majority of endometrial cancers, typifies the group of endometrial carcinomas that develop from atypical endometrial hyperplasia in the setting of excess estrogenic stimulation. In contrast, serous carcinomas are representative of endometrial tumors that occur in older women who have endometrial atrophy and lack the typical endometrial cancer risk factors reflecting unopposed estrogen exposure. Serous carcinomas are frequently associated with p53 abnormalities and appear to develop from a surface lesion termed endometrial intraepithelial carcinoma. Although serous carcinomas are rare, these highly aggressive tumors account for a disproportionate number of endometrial cancer deaths. Further delineation of the estrogen-dependent and estrogen-independent pathways of endometrial carcinogenesis may be useful in developing comprehensive chemopreventive approaches for endometrial cancer.