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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

          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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          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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            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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              Clinicopathologic findings in endometrial polyps.

              A study of endometrial polyps in biopsy specimens of symptomatic women showed 311 cases in a population of 1305 patients, an incidence of 23.8%. The highest incidence was seen in the fifth decade of life, and approximately one-fifth occurred after menopause. More than half of the subjects complained of metrorrhagia. Nearly half of the endometria exhibited proliferative changes; basal-type polyps accounted for only one-fifth of the total.
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                Author and article information

                Journal
                spmj
                Sao Paulo Medical Journal
                Sao Paulo Med. J.
                Associação Paulista de Medicina - APM (São Paulo, SP, Brazil )
                1516-3180
                1806-9460
                February 2020
                : 138
                : 1
                : 64-68
                Affiliations
                [2] Porto Alegre Rio Grande do Sul orgnameSanta Casa de Misericórdia de Porto Alegre orgdiv1Pathology Service Brazil
                [6] Porto Alegre Rio Grande do Sul orgnamePontifícia Universidade Católica do Rio Grande do Sul Brazil
                [4] Porto Alegre Rio Grande do Sul orgnameUniversidade Federal do Rio Grande do Sul Brazil
                [1] Porto Alegre Rio Grande do Sul orgnameUniversidade Federal de Ciências da Saúde de Porto Alegre orgdiv1Department of Gynecology and Obstetrics Brazil
                [3] Porto Alegre Rio Grande do Sul orgnameUniversidade Federal de Ciências da Saúde de Porto Alegre orgdiv1Department of Gynecology and Obstetrics Brazil
                [8] Porto Alegre Rio Grande do Sul orgnameUniversidade Federal de Ciências da Saúde de Porto Alegre orgdiv1Postgraduate Program on Pathology Brazil
                [7] Porto Alegre Rio Grande do Sul orgnameSanta Casa de Misericórdia de Porto Alegre orgdiv1Pathology Service Brazil
                [5] Porto Alegre Rio Grande do Sul orgnameUniversidade Federal do Rio Grande do Sul Brazil
                Article
                S1516-31802020000100064 S1516-3180(20)13800100064
                10.1590/1516-3180.2018.0346.r4.19112019
                e6f462d8-a0af-49c7-83f4-412c5127e496

                This work is licensed under a Creative Commons Attribution 4.0 International License.

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                Figures: 0, Tables: 0, Equations: 0, References: 20, Pages: 5
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                Categories
                Original Article

                Polyps,Tamoxifen,Menopause,Immunohistochemistry,Gynecology,Endometrium,Endometrial polyps,Postmenopause,Hormone therapy

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