Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mod Pathol. 2018 Jan;31(1):198-208. doi: 10.1038/modpathol.2017.74. Epub 2017 Oct 27.
Androgen-deprivation therapy has been the standard treatment for metastatic and locally advanced prostate cancer, but the majority of patients will progress to castration-resistant prostate cancer within 2-3 years. Unlike the case in breast cancer, no clinically validated biomarker has been used to predict the outcomes of androgen-deprivation therapy. To evaluate androgen-receptor splice variant-7 (AR-V7) detection in newly diagnosed advanced prostate cancer and describe the distinctive prognosis of this novel molecular subtype, this study retrospectively enrolled 168 newly diagnosed prostate cancer patients from 2003 to 2015 who received androgen-deprivation therapy. AR-V7 immunohistochemical staining was performed with a monoclonal antibody, and AR-V7 expression was determined using Immune-Reactive Score data. The association between nuclear AR-V7 expression and prognosis was determined. Multiple cause-specific Cox regression and stratified cumulative incidences were used to analyze the prognosis risk. Among the 168 patients, 32 (19%) were AR-V7-positive. Compared with the AR-V7-negative patients, the AR-V7-positive patients had significantly lower prostate-specific antigen response rates (P<0.001) to androgen-deprivation therapy and a much shorter time to castration-resistant prostate cancer (P<0.0001). In Kaplan-Meier analysis, the AR-V7-positive group showed markedly lower castration-resistant prostate cancer progression-free survival (P<0.0001) and much lower cancer-specific (P<0.0001) and overall survival (P<0.0001) both in all enrolled patients and in patients with metastases. AR-V7 positivity was a significant predictor of castration-resistant prostate cancer progression in multiple Cox regression (hazard ratio: 4.826; 95% CI: 2.960-7.869; P<0.001). AR-V7 immunohistochemical detection in newly diagnosed prostate cancer patients who are planning to receive androgen-deprivation therapy, especially those with metastases, is necessary and valuable for prognostic assessment. AR-V7-positive prostate cancer should be considered a novel prostate cancer subtype that should be distinguished upon initial biopsy. The main limitation of this study is its observational nature.
雄激素剥夺疗法一直是转移性和局部晚期前列腺癌的标准治疗方法，但大多数患者在 2-3 年内会进展为去势抵抗性前列腺癌。与乳腺癌不同，目前尚无经临床验证的生物标志物可用于预测雄激素剥夺疗法的结果。为了评估新诊断的晚期前列腺癌中雄激素受体剪接变体 7（AR-V7）的检测，并描述这种新型分子亚型的独特预后，本研究回顾性纳入了 2003 年至 2015 年期间接受雄激素剥夺疗法的 168 例新诊断的前列腺癌患者。采用单克隆抗体进行 AR-V7 免疫组织化学染色，并使用免疫反应评分数据确定 AR-V7 表达。确定核 AR-V7 表达与预后之间的关联。采用多因素特异性 Cox 回归和分层累积发生率分析预后风险。在 168 例患者中，有 32 例（19%）为 AR-V7 阳性。与 AR-V7 阴性患者相比，AR-V7 阳性患者对雄激素剥夺疗法的前列腺特异性抗原反应率明显较低（P<0.001），去势抵抗性前列腺癌的时间也明显缩短（P<0.0001）。在 Kaplan-Meier 分析中，AR-V7 阳性组的去势抵抗性前列腺癌无进展生存率明显较低（P<0.0001），癌症特异性生存率（P<0.0001）和总生存率（P<0.0001）也明显较低，在所有入组患者和转移性患者中均如此。在多因素 Cox 回归中，AR-V7 阳性是去势抵抗性前列腺癌进展的显著预测因子（危险比：4.826；95%CI：2.960-7.869；P<0.001）。在计划接受雄激素剥夺疗法的新诊断前列腺癌患者中进行 AR-V7 免疫组织化学检测，尤其是那些有转移的患者，对于预后评估是必要且有价值的。AR-V7 阳性的前列腺癌应被视为一种新的前列腺癌亚型，在初次活检时应加以区分。本研究的主要局限性在于其观察性性质。
