Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Eur Urol. 2014 Nov;66(5):851-60. doi: 10.1016/j.eururo.2014.02.058. Epub 2014 Mar 7.
Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed.
To examine the association between ERG expression at diagnosis and the risk of progression during AS.
DESIGN, SETTING, AND PARTICIPANTS: This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10-12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression.
Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events.
A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p<0.0001) and of the subgroups PSA progression (p<0.0001) and histopathologic progression (p<0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3-29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7-68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62-3.72; p<0.0001). The main limitation of this study is its observational nature.
In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes.
The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.
需要有强有力的生物标志物来识别接受主动监测（AS）的前列腺癌患者中具有高进展风险的患者。
研究 ERG 表达与 AS 期间进展风险之间的关联。
设计、设置和参与者：这项研究包括 265 名患者，他们在 2002 年至 2012 年期间在一个前瞻性维护的数据库中接受了前列腺特异性抗原（PSA）测量、临床检查和 10-12 个核心重新活检的 AS 随访。使用即用型试剂盒（抗 ERG，EPR3864）对诊断性石蜡包埋福尔马林固定切片进行 ERG 免疫组织化学染色。如果至少有一个肿瘤焦点显示 ERG 表达，则将男性定义为 ERG 阳性。
总体 AS 进展定义为临床进展：通过直肠指检和超声检查，临床肿瘤分类增加≥cT2b，和/或组织病理学进展：Gleason 评分升级，超过三个阳性核心或双侧阳性核心，和/或 PSA 进展：PSA 倍增时间<3 年。使用多原因特定 Cox 回归和分层累积发生率（Aalen-Johansen 方法）分析进展风险。有意治愈的治疗、观察等待和无进展死亡被视为竞争事件。
在完全诊断信息的 142 名 ERG 阴性患者中，有 121 名和在完全诊断信息的 123 名 ERG 阳性患者中，有 96 名。在竞争风险模型中，ERG 阳性组的总体 AS 进展发生率明显更高（p<0.0001），PSA 进展（p<0.0001）和组织病理学进展（p<0.0001）亚组也是如此。在 ERG 阴性组，2 年的总体 AS 进展累积发生率为 21.7%（95%置信区间 [CI]，14.3-29.1），而在 ERG 阳性组为 58.6%（95% CI，48.7-68.5）。在多 Cox 回归中，ERG 阳性是总体 AS 进展的显著预测因素（危险比：2.45；95% CI，1.62-3.72；p<0.0001）。本研究的主要局限性在于其观察性性质。
在我们的研究中，诊断时的 ERG 阳性可用于估计 AS 期间进展的风险。如果得到证实，ERG 状态可用于个体化 AS 计划。
组织生物标志物 ERG 可识别具有疾病进展风险增加的主动监测患者。
