Differences in estrogen and progesterone receptor expression in endometrial polyps and atrophic endometrium of postmenopausal women with and without exposure to tamoxifen

Abstract

Abstract.Postmenopausal women who use tamoxifen present with an increased incidence of endometrial alterations, such as polyps and hyperplasia, in addition to a higher risk of malignant endometrial neoplasms. Among these endometrial changes, polyps are the most common, with a pathogenesis associated with hormonal influence. The objective of this study was to compare the expression of estrogen receptors (ERs) and progesterone receptors (PRs) in endometrial polyps from tamoxifen users with that in endometrial polyps and the atrophic endometrium of postmenopausal tamoxifen non-users. Among women undergoing surgical hysteroscopy, 84 tamoxifen users with benign endometrial polyps were selected. This group was compared to 84 samples of atrophic endometrium and to 252 benign polyps from postmenopausal women who were not treated with tamoxifen. The expression of ER̸PR was assessed by immunohistochemical analysis, according to the percentage of stained cells, intensity of nuclear staining and final score. The polyps from tamoxifen users exhibited a higher expression of ER and PR in the glandular epithelium and stroma compared to the atrophic endometrium (P<0.0001). Compared to the polyps from women not treated with tamoxifen, tamoxifen users exhibited a higher PR expression in the epithelium (P=0.0014) and stroma (P=0.0056), with no difference in the expression of ER. In conclusion, endometrial polyps frequently exhibit an increase in ER expression, regardless of tamoxifen use. High levels of PR expression appear to be consistent with the estrogen agonist effects of tamoxifen.

Post hysteroscopic progesterone hormone therapy in the treatment of endometrial polyps

“… 6 Previous studies have suggested that short-acting or slowly released progesterone hormone in combination with hysteroscopic resection was significantly effective in preventing postoperative recurrence of endometrial polyp. 7 - 9 …”

Immunohistochemical expression of hormone receptors, Ki-67, endoglin (CD105), claudins 3 and 4, MMP -2 and -9 in endometrial polyps and endometrial cancer type I

“… 8 Their lipophilic structure allows estrogen to pass freely through the cell membrane and bind to the ER in the nucleus, controlling the expression of several genes, including those that encode PR and growth factors. 19 Exposure to estrogen unopposed by progesterone promotes the activation of oncogenes and the inactivation of tumor suppressor genes, impairing cell cycle regulation and leading to dysfunction of the proteins involved in tumor invasion and progression. 19 , 33 An imbalance between cell proliferation and apoptosis, influenced by the concentration of sex steroids, is thought to be one of the mechanisms underlying the development of endometrial disorders, either benign or malignant.…”

“… 19 Exposure to estrogen unopposed by progesterone promotes the activation of oncogenes and the inactivation of tumor suppressor genes, impairing cell cycle regulation and leading to dysfunction of the proteins involved in tumor invasion and progression. 19 , 33 An imbalance between cell proliferation and apoptosis, influenced by the concentration of sex steroids, is thought to be one of the mechanisms underlying the development of endometrial disorders, either benign or malignant. 15 , 34 , 35 Thus, determining endometrial hormone response in the normal endometrium, as well as in benign, premalignant, and malignant lesions is very important for the characterization of potentially malignant changes.…”

“…These findings suggest that EP have a higher sensitivity to estrogen and progesterone and may develop even in the presence of low serum hormone concentrations. 19 , 23 , 24 , 36 In this study, however, although EP and EC were associated with hormone hyperstimulation, ER concentration was significantly higher in women with a normal endometrium than in those with EP or EC (4.0+ [0.0;4.0+] b vs 2.5+ [1.0+;4.0+] a vs 1.0+ [0.0;4.0+] a , respectively; P <0.001). PR concentration, in turn, was higher in the normal endometrium than in EC (4.0+ [0.0;4.0+] b vs 2.0+ [0.0;4.0+] a , respectively; P <0.05).…”

The potential role of HER2 upregulation in metastatic breast cancer to the uterus: a case report

“…While the primary application of tamoxifen exploits its antagonistic effect on ER in the breast, its dual agonistic effect in the uterus has been shown to increase the risk for development of new leiomyoma, increase the size of existent uterine leiomyomas, and induce cystic and edematous changes as a result of elevated PR expression 13, 14, 15. Although IDC and ILC are known to metastasize to the common sites of the liver, lung, bone, peritoneal, and retroperitoneal spaces, it is likely because of proliferative changes in the endometrium with increased vascularization observed with tamoxifen exposure secondary to overexpression of PR that creates a “primed” hospitable environment for tumor seeding.…”