Endometrial carcinoma steroid hormones and receptors in relation to proliferation

Abstract: The significance of the hormonal milieu for endometrial changes is as well-known as its link with endometrial carcinoma. Unopposed oestradiol treatment is shown to increase the incidence for this cancer. Obesity leads to elevated levels of oestrogens and is a risk factor for endometrial carcinoma. An association between high tumour proliferation and prognosis is a general feature of human cancer. Tumour growth can be expressed as proliferation rate and flow cytometry (FCM) is a sensitive and reproducable method to estimate S-phase fraction (SPF) and ploidy level. Both parameters have been shown to correlate with prognosis. Sex steroid hormone levels were analysed together with clinical parameters, SPF, and receptors in established endometrial carcinoma.The study consisted of postmenopausal women with endometrial adeno­carcinoma. H ormones were analysed in 127 patients, 99 were analysed for FCM and 60 for oestrogen and progesterone receptors. RIA technique was used for hormone assay of oestrone, oestradiol, progesterone, androstenedione and testosterone plasma levels. The receptors were analysed with an immunohistochemical method, and SPF and ploidy level by flow cytometry.A wide range of oestrogen concentrations was found. Some patients had levels comparable to fertile women. Strong correlations were found between body mass index, weight and depth of uterine cavity. No relations were found between receptors and SPF, apart from oestrogen- receptor positive tumours having a lower SPF when compared with receptor negative tumours. The influence of oestradiol on tumour proliferation expressed as SPF was ambiguous. SPF was increased with higher oestradiol levels in the group of peri-diploid, well-differentiated tumours, while a negative correlation was found for the peri-diploid, moderately differentiated tumours. The aneuploid and poorly differenti­ated tumours had a high SPF regardless of oestradiol concentration. The association between progesterone concentration and SPF was of a more general nature. Progesterone above a threshold level was related to a lower SPF in well-differentiated and moderately differentiated tumours. Thus endogenous progesterone seems to play a role in controlling the tumour’s proliferation activity, in contrast to oestradiol, that had a role which did not appear to relate to proliferation activity in any specific direction. The only stimulative association was seen in well-differentiated tumours, but SPF was still below the mean value for all diploid tumours.