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

Ferreira Leão,Rogerio  Barros; Andrade,Liliana; Vassalo,Jose; Antunes ,Armando; Pinto‑Neto,Aarão; Costa‑Paiva,Lucia

doi:10.3892/mco.2013.180

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

Authors:
- Rogerio Barros Ferreira Leão
- Liliana Andrade
- Jose Vassalo
- Armando Antunes
- Aarão Pinto‑Neto
- Lucia Costa‑Paiva
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Affiliations: Department of Obstetrics and Gynecology, School of Medicine, State University of Campinas (UNICAMP), Campinas, 13083‑881 São Paulo, Brazil, Department of Pathological Anatomy, School of Medicine, State University of Campinas (UNICAMP), Campinas, 13083‑881 São Paulo, Brazil
Published online on: September 12, 2013 https://doi.org/10.3892/mco.2013.180
Pages: 1055-1060

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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.

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1.	Goldstein SR: Controversy about uterine effects and safety of SERMs: the saga continues. Menopause. 9:381–384. 2002. View Article : Google Scholar : PubMed/NCBI
2.	Mourits MJ, De Vries EG, Willemse PH, Ten Hoor KA, Hollema H and Van der Zee AG: Tamoxifen treatment and gynecologic side effects: a review. Obstet Gynecol. 97:855–866. 2001. View Article : Google Scholar : PubMed/NCBI
3.	Katzenellenbogen JA, O’Malley BW and Katzenellenbogen BS: Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell- and promotor-specific action of these hormones. Mol Endocrinol. 10:119–131. 1996.
4.	Osborne CK and Schiff R: Estrogen-receptor biology: continuing progress and therapeutic implications. J Clin Oncol. 23:1616–1622. 2005. View Article : Google Scholar : PubMed/NCBI
5.	Shang Y and Brown M: Molecular determinants for the tissue specificity of SERMs. Science. 295:2465–2468. 2002. View Article : Google Scholar : PubMed/NCBI
6.	Gielen SC, Kühne LC, Ewing PC, Blok LJ and Burger CW: Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study. Endocr Relat Cancer. 12:1037–1049. 2005. View Article : Google Scholar : PubMed/NCBI
7.	de Cremoux P: Hormone therapy and breast cancer. Bull Cancer. 98:1311–1319. 2011.(In French).
8.	Gielen SC, Santegoets LA, Hanifi-Moghaddam P, Burger CW and Blok LJ: Signaling by estrogens and tamoxifen in the human endometrium. J Steroid Biochem Mol Biol. 109:219–223. 2008. View Article : Google Scholar : PubMed/NCBI
9.	Curtis RE, Boice JD Jr, Shriner DA, Hankey BF and Fraumeni JF Jr: Second cancers after adjuvant therapy for breast cancer. J Natl Cancer Inst. 88:832–834. 1996. View Article : Google Scholar : PubMed/NCBI
10.	Deligdisch L, Kalir T, Cohen CJ, de Latour M, Le Bouedec G and Penault-Llorca F: Endometrial histopathology in 700 patients treated with tamoxifen for breast cancer. Gynecol Oncol. 78:181–186. 2000. View Article : Google Scholar : PubMed/NCBI
11.	Fisher B, Constantino JP, Redmond CK, Fisher ER, Wickerham DL and Cronin WM: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 86:527–537. 1994. View Article : Google Scholar
12.	Maugeri G, Nardo LG, Campione C and Nardo F: Endometrial lesions after tamoxifen therapy in breast cancer women. Breast J. 7:240–244. 2001. View Article : Google Scholar : PubMed/NCBI
13.	Mignotte H, Lasset C, Bonadona V, et al: Iatrogenic risk of endometrial carcinoma after treatment for breast cancer in a large French case-control study. Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC). Int J Cancer. 76:325–330. 1998.PubMed/NCBI
14.	Van Leeuwen FE, Benraadt J, Coebergh JW, et al: Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet. 343:448–452. 1994.PubMed/NCBI
15.	Dibi RP, Zettler CG, Pessini SA, Ayub AV, de Almeida SB and da Silveira GP: Tamoxifen use and endometrial lesions: hysteroscopic, histological, and immunohistochemical findings in postmenopausal women with breast cancer. Menopause. 16:293–300. 2009. View Article : Google Scholar
16.	Marttunen MB, Cacciatore B, Hietanen P, Pyrhönen S, Tiitinen A, Wahlström T and Ylikorkala O: Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women. Br J Cancer. 84:897–902. 2001. View Article : Google Scholar : PubMed/NCBI
17.	Belisário MS, Vassallo J, Andrade LA, Alvarenga M, Pinto GA and Monteiro IM: The expression of the hormone receptors in the endometrium and endometrial polyps in postmenopausal women and its relationship to body mass index. Maturitas. 53:114–118. 2006.PubMed/NCBI
18.	Inceboz US, Nese N, Uyar Y, et al: Hormone receptor expressions and proliferation markers in postmenopausal endometrial polyps. Gynecol Obstet Invest. 61:24–28. 2006. View Article : Google Scholar : PubMed/NCBI
19.	Sant’Ana de Almeida EC, Nogueira AA, et al: Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps and adjacent endometrium in postmenopausal women. Maturitas. 49:229–233. 2004.
20.	Lopes RG, Baracat EC, de Albuquerque Neto LC, Ramos JF, Yatabe S, Depesr DB and Lippi UG: Analysis of estrogen- and progesterone-receptor expression in endometrial polyps. J Minim Invasive Gynecol. 14:300–303. 2007. View Article : Google Scholar : PubMed/NCBI
21.	Cohen I, Beyth Y, Altaras MM, et al: Estrogen and progesterone receptor expression in postmenopausal tamoxifen-exposed endometrial pathologies. Gynecol Oncol. 67:8–15. 1997. View Article : Google Scholar
22.	McGurgan P, Taylor LJ, Duffy SR and O’Donovan PJ: Does tamoxifen therapy affect the hormone receptor expression and cell proliferation indices of endometrial polyps? An immunohistochemical comparison of endometrial polyps from postmenopausal women exposed and not exposed to tamoxifen. Maturitas. 54:252–259. 2006. View Article : Google Scholar
23.	Mourits MJ, Ten Hoor KA, van der Zee AG, Willemse PH, de Vries EG and Hollema H: The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium. J Clin Pathol. 55:514–519. 2002. View Article : Google Scholar : PubMed/NCBI
24.	Schwartz LB, Krey L, Demopoulos R, Goldstein SR, Nachtigall LE and Mittal K: Alterations in steroid hormone receptors in the tamoxifen-treated endometrium. Am J Obstet Gynecol. 176:129–137. 1997. View Article : Google Scholar : PubMed/NCBI
25.	Fons G, Hasibuan SM, van der Velden J and ten Kate FJ: Validation of tissue microarray technology in endometrioid cancer of the endometrium. J Clin Pathol. 60:500–503. 2007. View Article : Google Scholar : PubMed/NCBI
26.	Harvey JM, Clark GM, Osbome CK and Allred DC: Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 17:1474–1481. 1999.
27.	Holm S: A simple sequentially rejective multiple test procedure. Scand J Stat. 6:65–70. 1979.
28.	Shaffer JP: Multiple hypothesis testing. Ann Rev Psychol. 46:561–584. 1995. View Article : Google Scholar
29.	Elkas J, Armstrong A, Pohl J, Cuttitta F, Martínez A and Gray K: Modulation of endometrial steroid receptors and growth regulatory genes by tamoxifen. Obstet Gynecol. 95:697–703. 2000. View Article : Google Scholar : PubMed/NCBI
30.	Corley D, Rowe J, Curtis MT, Hogan WM, Noumoff JS and Livolsi VA: Postmenopausal bleeding from unusual endometrial polyps in women on chronic tamoxifen therapy. Obstet Gynecol. 79:111–116. 1992.PubMed/NCBI
31.	Kennedy MM, Baigrie CF and Manek S: Tamoxifen and the endometrium: review of 102 cases and comparison with HRT-related and non-HRT-related endometrial pathology. Int J Gynecol Pathol. 18:130–137. 1999. View Article : Google Scholar : PubMed/NCBI
32.	Green S and Chambon P: Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 4:309–314. 1988. View Article : Google Scholar : PubMed/NCBI
33.	Parker MG, Fawell SE, Lees JA, White R, Emmans CE and Danielian P: Function of estrogen receptor as a transcription factor: A target for antiestrogens. Origins of Human Cancer: A Comprehensive Review. Brugge J, Curran E and McCormick F: Cold Spring Harbor Laboratory Press; Cold Spring Harbor: pp. 667–674. 1991
34.	Brys M, Szyllo K, Romanowicz-Makowska H, Dobrowolski Z, Maslowska I and Krajewska W: Expression of estrogen and progesterone receptor genes in endometrium, myometrium and vagina of postmenopausal women treated with estriol. Sao Paulo Med J. 127:128–133. 2009.PubMed/NCBI
35.	Turashvili G, Leung S, Turbin D, et al: Inter-observer reproducibility of HER2 immunohistochemical assessment and concordance with fluorescent in situ hybridization (FISH): pathologist assessment compared to quantitative image analysis. BMC Cancer. 9:1652009. View Article : Google Scholar
36.	Turbin DA, Leung S, Cheang MC, et al: Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: a tissue microarray study of 3,484 cases. Breast Cancer Res Treat. 110:417–426. 2008. View Article : Google Scholar