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

详细信息    查看全文

• 作者：Mohammad A. Aleskandarany ; Rezvan Abduljabbar…
• 关键词：Breast cancer ; Androgen receptor ; METABRIC ; Molecular ; Clinical ; Outcome
• 刊名：Breast Cancer Research and Treatment
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：159
• 期：2
• 页码：215-227
• 全文大小：1,269 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217
• 卷排序：159

文摘

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.