Endometrial adenocarcinoma: beliefs and scepticism

The incidence of endometrial adenocarcinoma is high in North America and northern Europe, and low in Asia and Africa. This variance in frequency rates occurred in the late 1970s and its real cause has remained in question since. There is a widespread belief that endometrial adenocarcinomas associated with endometrial hyperplasia have a much better prognosis than those related to endometrial atrophy. This view is, in general terms, true but only because a high proportion of tumors arising from an atrophic endometrium are of serous/papillary, clear cell, or Grade 2-3 endometrioid carcinomas, in contrast to those developing from a hyperplastic endometrium, which are nearly all G1 endometrioid adenocarcinomas. These adenocarcinomas have, however, an excellent prognosis, no matter whether they are related to hyperplasia or atrophy, and taxonomically they form a single tumor group. In this regard, it is most reasonable to separate endometrial carcinomas into low- and high-grade tumors. The first are formed solely of G1 or "authentic" endometrioid adenocarcinomas, i.e., endometrioid neoplasms composed in their entirety of glandular elements without having traces of nonsquamous solid components. The high-grade tumors are formed of both endometrioid Grade 2-3 adenocarcinomas and nonendometrioid carcinomas-all of particularly aggressive behavior. The question of grading endometrioid adenocarcinomas in a precise and reproducible way becomes obvious. It is also believed that endometrial adenocarcinomas associated with endometrial hyperplasia are estrogen-primed, while those related to endometrial atrophy are deprived of hormonal stimulation. However, as we have shown in this laboratory recently, estrogen stimulation may be very common in endometrial neoplasms developing in an atrophic endometrium. For indeed most, if not all, postmenopausal atrophic endometria harboring adenocarcinomas contain actively proliferating glands, with high Ki-67 proliferation index, high epidermal growth factor receptor (EGFR) activity, high microvessel density (MVD), and rich in estrogen and progesterone receptors (ER and PR), indicative of a continuous low-level estrogenic stimulation. That there is a number of endometrial carcinomas that tend to develop in a milieu of antiestrogenic domination, following treatment for breast carcinoma, this may well represent a form of breast-endometrial hereditary disease and, certainly, merits further investigation.