Proliferative activity in postmenopausal endometrium: the lurking potential for giving rise to an endometrial adenocarcinoma

Abstract

Aims: To investigate proliferation in disease free postmenopausal endometrium and that harbouring endometrial adenocarcinoma-is there a dynamic, yet lurking, potential for atrophic endometrium to give rise to endometrial adenocarcinoma?

Material/methods: The study comprised 84 disease free endometria from asymptomatic postmenopausal women who had undergone hysterectomy for prolapse, and 50 endometrioid cell type endometrial adenocarcinomas with adjacent uninvolved postmenopausal endometrium. The non-neoplastic tissues were separated histologically into active, inactive, and mixed forms, although only the first two categories were studied immunohistochemically for oestrogen and progesterone receptors (ERs, PRs), epidermal growth factor receptor (EGFR), Ki-67, and angiogenic activity.

Results: All postmenopausal endometria were atrophic, but only 42 were inactive; of the remaining samples, 22 were weakly proliferative and 20 were mixed active and inactive. In contrast, the non-neoplastic component of 43 of the 50 endometrial adenocarcinomas examined was of the active form; four specimens were of the pure and 39 of the mixed form. Interestingly, high ER and PR expression was seen in active and inactive endometria, but only the former were EGFR positive and had high proliferative (Ki-67) and angiogenic activity. A similar trend was also shown by the non-neoplastic atrophic endometrium adjacent to endometrial adenocarcinoma.

Conclusions: At least half of the disease free postmenopausal atrophic endometria show a weak proliferative pattern, either diffuse or focal, probably as a response to continuous low level oestrogenic stimulation. These tissues have a latent, although very small, carcinogenic potential, as demonstrated by the immunohistochemical profile and their frequent association with adjacent endometrial adenocarcinoma.

Figure 1

The immunohistochemical profile of weakly proliferative postmenopausal non-neoplastic endometrium found adjacent to endometrioid adenocarcinoma: (A) high oestrogen receptor content, (B) high progesterone receptor content, (C) epidermal growth factor receptor positivity, (D) high Ki-67 proliferation activity, and (E) high microvessel density.