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Cited by 84Endometrial and Cervical Cancer TreatmentsEstrogen and related hormone effectsBreast Cancer Treatment Studies

Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival

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Kamal, A M, Bulmer, J N, DeCruze, S B, Stringfellow, H F, Martin-Hirsch, P, Hapangama, D K·2016·British Journal of Cancer
DOI 10.1038/bjc.2016.16PMC PMC4800292
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Abstract

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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  • In high-grade endometrial cancer, androgen receptor (AR) expression is downregulated.

    “In a recent study, Kamal et al. [86] reported that the expression of AR was downregulated in high-grade EC but elevated in metastases, raising the possibility that they might be a target for therapy.”

    From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [86]

  • In metastases of endometrial cancer, androgen receptor (AR) expression is elevated.

    “In a recent study, Kamal et al. [86] reported that the expression of AR was downregulated in high-grade EC but elevated in metastases, raising the possibility that they might be a target for therapy.”

    From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [86]

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Authors
Kamal, A. M., Bulmer, J. N., DeCruze, S. B., Stringfellow, H. F., Martin-Hirsch, P., & Hapangama, D. K.
Affiliations
  • University of Liverpool (GB)
  • Newcastle University (GB)
  • Liverpool Women's Hospital (GB)
  • Lancashire Teaching Hospitals NHS Foundation Trust (GB)
Corresponding author
Hapangama, D K
ORCID
Venue
British Journal of Cancer
Publisher
Springer Science and Business Media LLC
Published
2016-03
Volume
114
Issue
6
Pages
688-696
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
DOI
10.1038/bjc.2016.16
PMC
PMC4800292
OpenAlex
W2292133344
Cited by
84
References
1
Citations by year
2026: 6 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 15 · 2021: 5 · 2020: 14 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 3
FWCI
11.63
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • Wellbeing of Women (RG1487, RG1073)
  • Higher Committee for Education Development in Iraq
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
androgen receptor, endometrial cancer, postmenopausal endometrium, endometrial hyperplasia, progesterone receptor, estrogen receptor alpha, estrogen receptor beta, Ki-67 proliferation index, metastatic endometrial cancer, disease-free survival, prognostic factors, therapeutic target, high-grade endometrial cancer
MeSH terms
Adult, Aged, Endometrium, Epithelium, Female, Humans, Immunohistochemistry, Middle Aged, Receptors, Androgen, Receptors, Progesterone, Case-Control Studies, Endometrial Neoplasms, Postmenopause, Estrogen Receptor alpha, Estrogen Receptor beta

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