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      Androgen receptor expression in endometrial carcinoma and its correlation with clinicopathologic features

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          Abstract

          Objectives

          Recent evidence suggests a role of androgen receptor expression as a prognostic and therapeutic biomarker in endometrial carcinoma, therefore in the present study we aimed to evaluate the frequency of androgen expression in different subtypes of endometrial carcinoma and its association with clinic-pathologic features.

          Results

          18/89 (20.2%) cases of endometrial carcinoma showed positive androgen receptor expression. On the other hand, low, moderate and high androgen receptor expression was noted in 7/89 (7.9%), 10/89 (11.2%) and 1/89 (1.1%) cases respectively. 15/77 (19.48%) of endometrioid cancers and 3/7 (42.28%) cases of serous carcinoma showed androgen receptor expression; while none of the cases of clear cell or carcinosarcoma revealed androgen receptor expression. No significant association of androgen receptor expression with various clinicopathologic features of endometrial carcinoma was noted. We found that a significant subset of endometrial cancers express androgen receptor especially a serous cancers; therefore we suggest that androgen receptor expression testing should be done in endometrial carcinoma.

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          Type I and II endometrial cancers: have they different risk factors?

          Veronica Wendy Setiawan, Hannah P Yang, Malcolm C. Pike … (2013)
          Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m(2) increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.
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            Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival

            A M Kamal, J N Bulmer, S B Decruze … (2016)
            Background: Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described. Methods: The expression pattern and prognostic value of AR in relation to oestrogen (ERα and ERβ) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n=85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR. Results: Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P<0.001) and ERα (P=0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P<0.0001), PR (P<0.0001) and ERβ (P<0.035) compared with LGEC, whilst maintaining weak to moderate ERα. Unlike PR, AR expression in metastatic lesions was significantly (P=0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P<0.0001, P<0.0001, respectively). Conclusions: Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ERα and ERβ may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC.
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              Serum Estrogens and Estrogen Metabolites and Endometrial Cancer Risk among Postmenopausal Women.

              Louise Brinton, Britton Trabert, Garnet Anderson … (2016)
              Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogen metabolites.
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                Author and article information

                Contributors
                Atif Ali Hashmi: doc_atif2005@yahoo.com
                Zubaida Fida Hussain: zaib2009@yahoo.com
                Amna Qadri: lilac_docamna@yahoo.com
                Muhammad Irfan: Irfan.zaffar@lnh.edu.pk
                Sahar Ramzan: sahar.ramzan24@hotmail.com
                Naveen Faridi: Naveen.faridi@lnh.edu.pk
                Amir Khan:
                ORCID: http://orcid.org/0000-0002-8763-7690
                dramirkhan04@gmail.com
                Muhammad Muzzammil Edhi: Muhammad_edhi@brown.edu
                Journal
                Journal ID (nlm-ta): BMC Res Notes
                Journal ID (iso-abbrev): BMC Res Notes
                Title: BMC Research Notes
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1756-0500
                Publication date (Electronic): 10 May 2018
                Publication date PMC-release: 10 May 2018
                Publication date Collection: 2018
                Volume: 11
                Electronic Location Identifier: 289
                Affiliations
                [1 ]ISNI 0000 0004 0637 9066, GRID grid.415915.d, Liaquat National Hospital and Medical College, ; Karachi, Pakistan
                [2 ]Shaheed Zulfiqar Ali Institute of Science and Technology, Karachi, Pakistan
                [3 ]GRID grid.440459.8, Kandahar University, ; Kandahar, 3802 Afghanistan
                [4 ]ISNI 0000 0004 1936 9094, GRID grid.40263.33, Brown University, ; Providence, RI USA
                Author information
                http://orcid.org/0000-0002-8763-7690
                Article
                Publisher ID: 3403
                DOI: 10.1186/s13104-018-3403-9
                PMC ID: 5946473
                PubMed ID: 29747687
                SO-VID: 6cda2c78-99f4-4149-a428-584913655d4e
                Copyright © © The Author(s) 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 30 March 2018
                Date accepted : 7 May 2018
                Categories
                Subject: Research Note
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Medicine
                Keywords: androgen receptor,endometrial cancer,endometrioid carcinoma,serous carcinoma,carcinosarcoma
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: androgen receptor, endometrial cancer, endometrioid carcinoma, serous carcinoma, carcinosarcoma

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