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.