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      Immunohistochemical assessment of symptomatic postmenopausal endometrial polyps in tamoxifen users and nonusers: a case control study

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          ABSTRACT

          BACKGROUND:

          Endometrial polyps are common in postmenopausal women, and the effect of tamoxifen use (a risk factor for endometrial polyps) on their pathogenesis is unclear.

          OBJECTIVES:

          To evaluate the expression of hormone receptors and markers for proliferation/apoptosis (Ki-67 and Bcl-2) in endometrial polyps in postmenopausal users and nonusers of tamoxifen.

          DESIGN AND SETTING:

          Cross-sectional analytical study in a tertiary-level academic hospital.

          METHODS:

          46 women (14 tamoxifen users and 32 nonusers) with postmenopausal bleeding underwent hysteroscopic resection of endometrial polyps. Polyp samples were immunohistochemically assessed for detection of Ki-67, Bcl-2 and estrogen and progesterone receptors.

          RESULTS:

          Analysis on the glandular component of the polyps revealed progesterone receptor expression in the polyps of 96.9% of the nonusers of tamoxifen, and 92.3% of the tamoxifen users (P = 0.499). All polyps in nonusers and 92.3% of those in users were also positive for estrogen receptors (P = 0.295). Ki-67 was expressed in 75% of the polyps in the tamoxifen users and 82.8% of those in the nonusers. All endometrial polyps expressed Bcl-2.

          CONCLUSIONS:

          The immunohistochemical analysis on endometrial polyps demonstrated that, although tamoxifen is considered to be a risk factor for endometrial polyps, there were no significant differences in the expression of hormone receptors between users and nonusers of tamoxifen. There were no between-group differences in Ki-67 and Bcl-2 expression, and all patients displayed inhibition of apoptosis by Bcl-2, thus supporting the theory that polyps develop due to inhibition of apoptosis, and not through cell proliferation.

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          Most cited references25

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          The differential expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67 in endometrial polyps.

          To obtain a greater understanding of the pathogenesis of endometrial polyps and to gain insight into which factors play a pivotal role in their growth. Retrospective analysis of archived paraffin-embedded specimens. St James's University Hospital. Thirty secretory phase endometrial samples, 10 secretory phase endometrial polyps, 8 proliferative phase endometrial samples and 10 proliferative phase endometrial polyps. Immunohistochemistry was used to characterise the expression of oestrogen and progesterone receptors, Bcl-2 and Ki67 in cycling endometrium and phase-matched endometrial polyps. Patterns of expression were compared between the polyps and the endometrium. The expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67. Three significant differences were found between the endometrium and the polyps. Polyps taken from the proliferative phase of the cycle displayed significantly elevated expression of Bcl-2 and weak or no expression of progesterone receptors. Secretory phase polyps displayed an elevated expression of oestrogen receptors. A localised increase in Bcl-2 expression and consequential decline or cessation of apoptosis is an important mechanism underlying the pathogenesis of endometrial polyps. Elevated Bcl-2 expression results in failure of the polyp tissue from undergoing normal cyclical apoptosis during the late secretory phase. This may mean the polyp is not shed along with the rest of the endometrium during menstruation.
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            Estrogen and progesterone receptor expression in endometrial polyps.

            Endometrial polyps are a frequent cause of abnormal uterine bleeding, but their pathogenesis is poorly understood. This study was undertaken to investigate if endometrial polyps result from localized overexpression of estrogen receptors (ERs) or reduced expression of progesterone receptors (PRs). Fourteen cases of endometrial polyps, in which normal cycling endometrium was also present on the same slide, were immunostained for ERs and PRs. Percentages of positive cells in glands and stroma for each receptor were subjectively assessed to the nearest 5%. The intensity of staining was recorded on a scale from 1+ to 4+. The level and intensity of staining in polyps were compared with the staining in normal endometrium. Fewer stromal cells in polyps expressed ERs and PRs compared with cycling endometrium (% ER = 55.9 +/- 25.8 vs. 74.3 +/- 25.8, p = 0.03; % PR = 56.1 +/- 28.2 vs. 87.5 +/- 10.1, p = 0.002). Stroma in polyps also had significantly reduced intensity of staining for PRs, but not for ERs (intensity PR = 2.7 +/- 1.4 vs. 3.5 +/- 0.7, p = 0.015; intensity ER = 2.1 +/- 0.7 vs. 2.4 +/- 0.8, p = 0.45). There were no significant differences in expression of ERs and PRs in the endometrial glands in endometrial polyps compared with normal endometrium (% ER = 75.4 +/- 32.5 vs. 70.7 +/- 39.2. p = 0.25; % PR = 79.6 +/- 32.8 vs. 80.4 +/- 34.4, p = 0.8; intensity ER = 2.7 +/- 0.9 vs. 2.4 +/- 1, p = 0.15; intensity PR = 2.9 +/- 1.4 vs. 3.4 +/- 0.7, p = 0.15). We conclude that endometrial polyps may result from a decrease in ER and PR expression in stromal cells. Because of these receptor-negative stromal cells, endometrial polyps may be relatively insensitive to cyclic hormonal changes.
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              Apoptosis: a programmed cell death involved in ovarian and uterine physiology.

              Apoptosis is a form of programmed cell death which occurs through the activation of a cell-intrinsic suicide machinery. The biochemical machinery responsible for apoptosis is expressed in most, if not all, cells. Contrary to necrosis, an accidental form of cell death, apoptosis does not induce inflammatory reaction noxious for the vicinity. Apoptosis is primarily a physiologic process necessary to remove individual cells that are no longer needed or that function abnormally. Apoptosis plays a major role during development, homeostasis. Many stimuli can trigger apoptotic cell death, but expression of genes can modulate the sensibility of the cell. The aim of this review is to summarise current knowledge of the molecular mechanisms of apoptosis and its roles in human endometrium and ovary physiology.
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                Author and article information

                Contributors
                Role: conception and design of study, data collection, data analysis and interpretation, statistical analysis and manuscript preparation;
                Role: conception and design of study, manuscript preparation, data collection and data analysis and interpretation;
                Role: conception and design of study, manuscript preparation and data collection;
                Role: manuscript preparation, statistical analysis and data analysis and interpretation;
                Role: manuscript preparation, data collection and data analysis and interpretation;
                Role: manuscript preparation, data collection and statistical analysis;
                Role: conception, manuscript preparation and data collection;
                Role: manuscript preparation, data collection and statistical analysis.
                Journal
                Sao Paulo Med J
                Sao Paulo Med J
                Sao Paulo Med J
                São Paulo Medical Journal
                Associação Paulista de Medicina - APM
                1516-3180
                1806-9460
                23 March 2020
                2020
                : 138
                : 1
                : 64-68
                Affiliations
                [I ] originalMD, PhD. Professor, Department of Gynecology and Obstetrics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA); and Professor, Gynecology and Obstetrics Service, Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre (RS), Brazil.
                [II ] originalMD, PhD. Pathologist, Pathology Service, Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre (RS), Brazil.
                [III ] originalMD, PhD. Professor, Department of Gynecology and Obstetrics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA); and Professor, Gynecology and Obstetrics Service, Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre (RS), Brazil.
                [IV ] originalMD. Undergraduate Student, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil.
                [V ] originalUndergraduate Medical Student, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil.
                [VI ] originalUndergraduate Medical Student, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre (RS), Brazil.
                [VII ] originalMD. Pathologist, Pathology Service, Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre (RS), Brazil.
                [VIII ] originalPhD. Epidemiologist, Postgraduate Program on Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre (RS), Brazil.
                Author notes
                Address for correspondence: Raquel Papandreus Dibi. Rua Dr. Vale, 595/303, Floresta - Porto Alegre (RS) - Brasil. CEP 90560-010. Tel. (+55 51) 3214-8000. E-mail: rpdibi@ 123456gmail.com

                Authors’ contributions: All authors approved the final version of the manuscript to be published

                Conflict of interest: None

                Article
                10.1590/1516-3180.2018.0346.R4.19112019
                9673849
                32215462
                e6f462d8-a0af-49c7-83f4-412c5127e496
                © 2022 by Associação Paulista de Medicina

                This is an open access article distributed under the terms of the Creative Commons license.

                History
                : 03 August 2018
                : 31 October 2019
                : 19 November 2019
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 20, Pages: 5
                Categories
                Original Article

                polyps,tamoxifen,menopause,immunohistochemistry,gynecology,endometrium,endometrial polyps,postmenopause,hormone therapy

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