Estradiol and progesterone receptors in normal and neoplastic endometrium: Correlations between receptors, histopathological examinations and clinical responses under progestin therapy

Abstract

AbstractHaving examined the steroid receptor (SR)' system in normal and neoplastic endometrium from pre‐and postmenopausal women, we investigated the effect of progestin therapy on estrogen and progestin receptors in neoplastic endometrium with respect to histopathological changes and clinical responses of the lesions. In normal endometrium of premenopausal women the estrogen receptor (ER) maximum occurred just before the estradiol (E) peak which is associated with a decrease in ER. In pre‐and postmenopausal women, a high progesterone receptor (PR) value was never associated with a high ER value although in postmenopausal women, PR was only detected when the ER level was high and when there was histological evidence of estrogenic influence. In neoplastic endometrium, a high degree of histological differentiation was associated with simultaneous low ER and high PR values, and vice‐versa. Progestin therapy results in virtually no change either in ER level or in pathological state of the lesions where PR was initially undetectable. In contrast, a positive clinical response was observed in a PR‐positive lesion revealing a differentiated histological type. The effect of P therapy is a fall in both ER and PR to a low level for the former and an undetectable level for the latter. The reasons for PR disappearance involve a nuclear translocation (detected 4 to 8 h after treatment) and a non‐replenishment of PR. Since the clinically responding patients were those with PR and ER positive lesions, the relationship between the presence of PR and a differentiated histological state could reflect the hormonal sensitivity of the tissue. These data also suggest that the effectiveness of P therapy is due to a redifferentiation and to a reduction of the estrogen‐dependent growth of neoplastic endometrial cells.