Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Eur Urol Focus. 2018 Dec;4(6):818-824. doi: 10.1016/j.euf.2017.02.016. Epub 2017 Mar 11.
ETS-related gene (ERG) oncogenic activation is the most common genomic alteration in prostate cancer (CaP) although it occurs less frequently in African American (AA) versus Caucasian (CA) patients, and the potential role of ERG as a prognostic marker has not been confirmed.
This study was conducted to confirm strong racial variation in the prevalence of ERG oncoprotein expression and to examine ERG oncoprotein expression, race, and body mass index as independent and joint predictors of CaP biochemical recurrence (BCR) following radical prostatectomy (RP).
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of CA and AA CaP patients enrolled at Walter Reed National Military Medical Center, who donated clinically annotated, whole-mounted, prostatectomy specimens between 1994 and 2014 following RP, was conducted.
Kaplan-Meier (KM) estimation curves and multivariable Cox proportional hazards models were used to examine time to BCR as a function of ERG status, patient race, and obesity.
Among 930 eligible patients (36.1% AA and 63.9% CA), with 155 (16.7%) BCR events and a median follow-up time of 5.1 yr, ERG oncoprotein expression was significantly less prevalent in index tumors of AA versus CA patients (23.2% vs 49.3%; p<0.0001). KM curves showed significantly poorer BCR-free survival for CA patients with ERG-negative index tumors but not for AA patients. Race-stratified multivariable analyses revealed a significant association between ERG-negative index tumors and poorer BCR-free survival among CA patients (hazards ratio=1.67, confidence interval=1.07, 2.61; p=0.024). Less heterogeneity in ERG expression among AA patients may reduce the ability to show its association with BCR.
Striking racial variation in ERG oncoprotein expression was confirmed. A novel observation was the importance of index tumor ERG-negative status in predicting CaP progression for CA patients.
ETS-related gene (ERG) typing of tumors may be useful in prognosticating prostate cancer aggressiveness.
ETS 相关基因（ERG）致癌激活是前列腺癌（CaP）最常见的基因组改变，尽管它在非裔美国人（AA）与高加索人（CA）患者中的发生率较低，并且 ERG 作为预后标志物的潜在作用尚未得到证实。
本研究旨在证实 ERG 癌蛋白表达存在明显的种族差异，并研究 ERG 癌蛋白表达、种族和体重指数作为前列腺癌根治性前列腺切除术后（RP）生化复发（BCR）的独立和联合预测因子。
设计、地点和参与者：本研究为回顾性队列研究，纳入了 1994 年至 2014 年间在沃尔特·里德国家军事医疗中心接受 RP 治疗的 CA 和 AA 前列腺癌患者，这些患者捐献了临床注释的、全层前列腺切除术标本。
采用 Kaplan-Meier（KM）估计曲线和多变量 Cox 比例风险模型，研究 ERG 状态、患者种族和肥胖对 BCR 的影响。
在 930 名符合条件的患者中（36.1%为 AA，63.9%为 CA），有 155 名（16.7%）发生 BCR 事件，中位随访时间为 5.1 年，AA 患者的指数肿瘤中 ERG 癌蛋白表达明显低于 CA 患者（23.2%比 49.3%；p<0.0001）。KM 曲线显示，CA 患者 ERG 阴性指数肿瘤的 BCR 无复发生存率明显较差，但 AA 患者则不然。种族分层多变量分析显示，CA 患者 ERG 阴性指数肿瘤与 BCR 无复发生存率较差之间存在显著关联（风险比=1.67，置信区间=1.07，2.61；p=0.024）。AA 患者 ERG 表达的异质性较小，可能降低了其与 BCR 相关的能力。
本研究证实了 ERG 癌蛋白表达存在明显的种族差异。一个新的发现是，指数肿瘤 ERG 阴性状态对 CA 患者预测前列腺癌进展的重要性。
肿瘤 ETS 相关基因（ERG）分型可能有助于预测前列腺癌的侵袭性。
