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Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis

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Abstract

Differential prognostic roles of Androgen Receptor (AR) have been proposed in breast cancer (BC) depending on tumour oestrogen receptor (ER) status. This study aimed to evaluate the prognostic and/or predictive significance of AR expression in invasive BC. In this study AR expression was studied on a large (n = 1141) consecutive series of early-stage (I–III) BC using tissue microarray and immunohistochemistry (IHC). AR mRNA expression was assessed in a subset of cases. The prognostic impact of AR mRNA expression was externally validated using the online BC gene expression data sets (n = 25 data sets, 4078 patients). Nuclear AR IHC expression was significantly associated with features of good prognosis including older age, smaller tumour size, lower grade and lobular histology particularly in the ER-positive tumours. AR was associated with ER-related markers GATA3, FOXa1, RERG and BEX1. Negative association was observed with HER2, p53, Ki67, TK1, CD71 and AGTR1. AR Overexpression was associated with longer survival (p < 0.001), independent of tumour size, grade, stage [p = 0.033, hazard ratio (HR) = 0.80 95 % CI = 0.64–0.98]. Similar associations were maintained in ER+ tumours in univariate and multivariate analysis (p < 0.01) both in patients with and without adjuvant endocrine or chemotherapy. AR mRNA expression showed significant association with tumour grade, molecular subtypes, and longer 10 and 15 years survival in luminal BC. In the external validation cohorts, AR gene expression data were associated with improved patients’ outcome (p < 0.001, HR = 0.84, 95 % CI 0.79–0.90). AR is not only an independent prognostic factor in ER-positive luminal BC but is also expressed in ER-negative tumours. AR could act as a molecular target in patients with ER-positive disease predicting response to adjuvant therapy.

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Acknowledgment

MA Aleskandarany and Maria Diez-Rodriguez are funded by the University of Ha’il, KSA.

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Authors and Affiliations

  1. Division of Cancer and Stem Cells, Molecular Pathology Research Unit, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK

    Mohammad A. Aleskandarany, Dena Jerjees, Maria Diez-Rodriguez, Andrew R. Green, Ian O. Ellis & Emad A. Rakha

  2. Department of Pathology, Faculty of Medicine, Menoufia University, Al Minufiyah, Egypt

    Mohammad A. Aleskandarany & Emad A. Rakha

  3. Department of Oncology, Azadi Teaching Hospital, Duhok, Kurdistan, 1014 AM, Iraq

    Rezvan Abduljabbar

  4. Molecular Diagnostics and Personalised Therapeutics Unit, University of Ha’il, Ha’il, Saudi Arabia

    Ibraheem Ashankyty & Ahmed Elmouna

  5. Department of Surgery and Cancer, Imperial College London, London, UK

    Simak Ali & Laki Buluwela

  6. Centre for the Cambridge Experimental Cancer Medicine Centre (ECMC) and Cambridge Breast Cancer Research Unit, Cambridge, UK

    Carlos Caldas

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  1. Mohammad A. Aleskandarany
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  2. Rezvan Abduljabbar
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Correspondence to Mohammad A. Aleskandarany.

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Mohammad A. Aleskandarany and Rezvan Abduljabbar are first joint authors.

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Aleskandarany, M.A., Abduljabbar, R., Ashankyty, I. et al. Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis. Breast Cancer Res Treat 159, 215–227 (2016). https://doi.org/10.1007/s10549-016-3934-5

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  • DOI: https://doi.org/10.1007/s10549-016-3934-5

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