The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors, progesterone receptors, and Ki-67 antigen.

Objective: To enlighten the early response of endometrium to tamoxifen by assessing the expression of estrogen receptors, progesterone receptors, Ki-67, and the histological response in endometria from normal postmenopausal women treated for 21 days with tamoxifen.

Methods: A total of 40 women, scheduled to undergo vaginal hysterectomy because of uterine prolapse, were randomly assigned to the tamoxifen group (20 mg/day; 20 women) or the control group (20 women). Samples were obtained from the upper and the lower thirds of the uterine cavity. Standard immunohistochemical staining of estrogen and progesterone receptors and of Ki-67 was performed on frozen sections. Staining was assessed using semiquantitative immunoreactivity scores.

Results: Simple endometrial hyperplasia was diagnosed in 18 of the 20 samples exposed to tamoxifen compared with only 2 of the 20 controls ( P< 0.0005). Staining was increased in both the epithelium and stroma in the tamoxifen samples, a difference that was significant for estrogen receptors in glandular epithelium (180 +/- 80 v 110 +/- 110; P< 0.05). Also, Ki-67 antigen was expressed more frequently in both glandular epithelium ( P< 0.05) and stroma ( P< 0.05) in the tamoxifen samples.

Conclusions: Tamoxifen rapidly up-regulated the cell proliferation markers, an effect that was associated with enhanced growth as confirmed by increased expression of estrogen receptors and Ki-67, in addition to a high incidence of glandular hyperplasia.