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

Tregón, María-Luisa MD1; Blümel, Juan-Enrique MD2; Tarín, Juan J. PhD3; Cano, Antonio MD1


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.

Design: 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.

From the 1Department of Pediatrics, Obstetrics and Gynecology, Facultad de Medicina, Universidad de Valencia, Valencia, Spain, the 2Climacteric Unit, Barros Luco-Tradeau Hospital, Santiago, Chile, and the 3Department of Functional Biology and Physical Anthropology, Facultad de Ciencias Biológicas, Universidad de Valencia, Valencia, Spain.

Received April 24, 2002; revised and accepted August 27, 2002.

This work was supported by grants 1FD97-1035-C02-01 from the Comisión Interministerial de Ciencia y Tecnología, Madrid, Spain, and the European Union, 00/0960 from Fondo de Investigación Sanitaria, Madrid, Spain, and GV99-6-1-04 from the Consellería de Cultura, Educació i Ciència, Generalitat Valenciana, Valencia, Spain.

Address correspondence to Antonio Cano, MD, Department of Pediatrics, Obstetrics and Gynecology, Facultad de Medicina, Av. Blasco Ibáñez 17, E-46010 Valencia, Spain. E-mail:

©2003The North American Menopause Society