Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy

Abstract

The cell proliferation-associated antigen Ki 67 and the immunohistochemical content of oestrogen receptors (ER), progesterone receptors AB (PRAB) and progesterone receptors B (PRB) were evaluated in leiomyomata and adjacent myometrium during the menstrual cycle and in leiomyomata under gonadotrophin-releasing hormone agonist (GnRHa) therapy. The proliferative status of muscular cells was measured by evaluating the percentage of nuclei staining positive for Ki 67 (proliferation index). Quantitative analysis (QH-score) was carried out using advanced stereographic computer technology to investigate ER, PRAB and PRB. Leiomyoma and myometrial biopsies were taken from 30 patients undergoing hysterectomy or myomectomy because of symptomatic leiomyomata (subgroup I). Leiomyoma biopsies were taken from 10 patients suffering from symptomatic submucosal leiomyomata, after 2 month GnRH therapy (subgroup II). During the secretory phase, the proliferation index (Ki 67) was found to be higher in leiomyomata than in myometrium, but the difference was not significant. Oestrogen receptor content was significantly higher in leiomyomata than in myometrium only during the proliferative phase of the cycle. PRAB and PRB content were found to be higher in leiomyomata than in adjacent myometrium with a statistically significant dominance of PRAB over PRB. Under GnRHa therapy, a dramatic decrease was observed in PRAB and B content as well as Ki 67 but ER content remained comparable with the results obtained during the menstrual cycle. The results suggest that leiomyomata may be under the influence of progesterone which may play a major role in their growth.

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

“…Stained TMA slides were graded jointly by two pathologists (RF, CB). A modified visual semiquantification method was used as previously described, 24 using a two-score system for immunointensity (II) and immunopositivity (IP). II and IP scores were summated.…”

Medical Management of Uterine Fibroids

“…Compared with the surrounding endometrium, uterine myoma has a high concentration of progesterone receptors [8,9]. Mifepristone, onapristone, and ZK 230211 are pure progesterone receptor modulators.…”

“…Because the tumors are hormonally dependent, develop during the reproductive period, and are suppressed by menopause, current medical treatments involve mainly hormonal manipulations [7]. Studies have shown the presence of estrogen and progesterone receptors with higher concentrations in myomas than in the surrounding endometrium [8,9]. Progesterone seems to have a dual effect on myomas by altering local growth factors.…”

Gynaecological uses of a new class of steroids: the selective progesterone receptor modulators

“…Mitotic activity is maximal during the luteal phase [59]. Several studies have shown an up-regulation of PR in uterine leiomyomata compared with normal adjacent myometrium at mRNA and protein levels [60].…”

“…During the luteal phase, in the primate uterus, progesterone inhibits estrogen induced mitotic activity in the functional zones of the endometrial epithelium but shows some stimulatory effect on both the basalis and endometrial angiogenesis [7]. Progesterone can also play a key role on growth of benign smooth muscles tumours from uterine myometrium [8][9][10]. In normal breast epithelial cells, progesterone has important mitogenic properties with a peak of a mitotic activity during the luteal phase [11].…”