title: Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis.
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.
authors: 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. mohammed.aleskandarany@nottingham.ac.uk.|Department of Pathology, Faculty of Medicine, Menoufia University, Al Minufiyah, Egypt. mohammed.aleskandarany@nottingham.ac.uk.
authors: Mohammad A
authors: MA
authors: Aleskandarany
authors: Department of Oncology, Azadi Teaching Hospital, Duhok, Kurdistan, 1014 AM, Iraq.
authors: Rezvan
authors: R
authors: Abduljabbar
authors: Molecular Diagnostics and Personalised Therapeutics Unit, University of Ha'il, Ha'il, Saudi Arabia.
authors: Ibraheem
authors: I
authors: Ashankyty
authors: Molecular Diagnostics and Personalised Therapeutics Unit, University of Ha'il, Ha'il, Saudi Arabia.
authors: Ahmed
authors: A
authors: Elmouna
authors: 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.
authors: Dena
authors: D
authors: Jerjees
authors: Department of Surgery and Cancer, Imperial College London, London, UK.
authors: Simak
authors: S
authors: Ali
authors: Department of Surgery and Cancer, Imperial College London, London, UK.
authors: Laki
authors: L
authors: Buluwela
authors: 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.
authors: Maria
authors: M
authors: Diez-Rodriguez
authors: Centre for the Cambridge Experimental Cancer Medicine Centre (ECMC) and Cambridge Breast Cancer Research Unit, Cambridge, UK.
authors: Carlos
authors: C
authors: Caldas
authors: 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.
authors: Andrew R
authors: AR
authors: Green
authors: 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.
authors: Ian O
authors: IO
authors: Ellis
authors: 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.|Department of Pathology, Faculty of Medicine, Menoufia University, Al Minufiyah, Egypt.
authors: Emad A
authors: EA
authors: Rakha
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060787:Neoplasm Grading; D011379:Prognosis; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D046888:Tissue Array Analysis; D047368:Tumor Burden
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D011960:Receptors, Estrogen
keywords: Androgen receptor; Breast cancer; Clinical; METABRIC; Molecular; Outcome