Androgen receptor isoforms expression in benign prostatic hyperplasia and primary prostate cancer

The role of molecular changes in the androgen receptor (AR) as AR variants (AR-Vs) is not clear in the pathophysiology of benign prostatic hyperplasia (BPH) and hormone-naïve PCa. The aim of the current work was to identify the presence of AR isoforms in benign tissue and primary PCa, and to evaluate the possible association with tumor aggressiveness and biochemical recurrence in primary PCa. The mRNA levels of full length AR (AR-FL) and AR-Vs (AR-V1, AR-V4 and AR-V7) were measured using RT-qPCR. The protein expression of AR-FL (AR-CTD and AR-NTD) and AR-V7 were evaluated by the H-Score in immunohistochemistry (IHC). All investigated mRNA targets were expressed both in BPH and PCa. AR-FL mRNA levels were similar in both groups. AR-V4 mRNA expression showed higher levels in BPH, and AR-V1 and AR-V7 mRNA expression were higher in PCa. The AR-V7 protein showed a similar H-Score in both groups, while AR-CTD and AR-NTD were higher in nuclei of epithelial cells from BPH. These results support the assumption that these constitutively active isoforms of AR are involved in the pathophysiology of primary PCa and BPH. The role of AR-Vs and their possible modulation by steroid tissue levels in distinct types of prostate tumors needs to be elucidated to help guide the best clinical management of these diseases.

雄激素受体（androgen receptor, AR）的分子变化以其变异体（AR variants, AR-Vs）的形式，在良性前列腺增生（benign prostatic hyperplasia, BPH）与激素初治前列腺癌（hormone-naïve PCa）的病理生理过程中所发挥的作用尚未明确。本研究旨在鉴定良性组织与原发性前列腺癌（primary PCa）中雄激素受体亚型的表达情况，并评估其与原发性前列腺癌肿瘤侵袭性及生化复发的潜在关联。本研究采用RT-qPCR检测了全长雄激素受体（full length AR, AR-FL）与AR变异体（AR-V1、AR-V4及AR-V7）的mRNA水平；通过免疫组织化学（immunohistochemistry, IHC）的H评分，评估了AR-FL（AR-CTD与AR-NTD）及AR-V7的蛋白表达情况。所有检测的mRNA靶标均在BPH与PCa组织中有所表达。两组样本的AR-FL mRNA水平无显著差异。AR-V4的mRNA表达在BPH组织中更高，而AR-V1与AR-V7的mRNA表达在PCa组织中更高。AR-V7蛋白的H评分在两组中无显著差异，而AR-CTD与AR-NTD在BPH上皮细胞的细胞核中表达水平更高。上述结果支持以下假设：此类组成型活性雄激素受体亚型参与了原发性前列腺癌与良性前列腺增生的病理生理过程。AR变异体的作用及其在不同类型前列腺肿瘤中受类固醇组织水平调控的潜在机制仍有待阐明，以助力指导上述疾病的最优临床管理策略。