Department of Surgery/Division of Urology, McGill University Health Center, Montreal, Quebec, H3G 1A4 Canada.
Eur Urol. 2011 Mar;59(3):407-14. doi: 10.1016/j.eururo.2010.11.026. Epub 2010 Nov 26.
The TMPRSS2:ERG fusion is both prevalent and unique to prostate cancer (PCa) and has great potential for noninvasive diagnosis of PCa in bodily fluids.
To evaluate the specificity and sensitivity of the TMPRSS2:ERG fusion in urine from diverse clinical contexts and to explore potential clinical applications.
DESIGN, SETTING, AND PARTICIPANTS: A total of 101 subjects were enrolled in 2008 from urologic oncology clinics to form three study groups: 44 PCa free, 46 confirmed PCa, and 11 negative prostate biopsies. The PCa-free group included females, healthy young men, and post-radical prostatectomy (RP) patients. The confirmed PCa group was composed of patients under active surveillance, scheduled for treatment, or with metastatic disease.
Urine was collected after attentive digital rectal exam (DRE) and coded to blind group allocation for laboratory test. RNA from urine sediments was analyzed using a panel of four TMPRSS2:ERG fusion markers with quantitative polymerase chain reaction (qPCR).
Our fusion markers demonstrated very high technical specificity and sensitivity for detecting a single fusion-positive cancer cell (VCaP) in the presence of at least 3000 cells in urine sediments. In clinical analysis, there were no fusion-positive samples in the PCa-free group (0 of 44 samples), while there were 16 of 46 (34.8%) fusion-positive samples in the confirmed PCa group. The fusion incidence varied significantly among the three PCa subgroups. The clinical sensitivity increased to 45.4% in cancer patients prior to treatments. The fusion markers were detected in 2 of 11 (18.2%) biopsy-negative patients, suggesting potentially false negative biopsies. This study is not prospective and is limited in sample sizes.
Our novel panel of TMPRSS2:ERG fusion markers provided a very specific and sensitive tool for urine-based detection of PCa. Theses markers can potentially be used to diagnose patients with PCa who have negative biopsies.
TMPRSS2:ERG 融合不仅普遍存在于前列腺癌（PCa）中，而且在体液中对 PCa 的非侵入性诊断具有巨大的潜力。
评估 TMPRSS2:ERG 融合在不同临床背景下尿液中的特异性和敏感性，并探索其潜在的临床应用。
设计、设置和参与者：2008 年，共有 101 名受试者从泌尿科肿瘤诊所入组，形成三组研究：44 名前列腺癌阴性、46 名确诊前列腺癌和 11 名前列腺活检阴性。前列腺癌阴性组包括女性、健康年轻男性和前列腺根治术后（RP）患者。确诊前列腺癌组由主动监测、计划治疗或转移性疾病的患者组成。
尿液在精细的直肠指检（DRE）后采集，并编码以对实验室检测进行分组盲法。使用一组四个 TMPRSS2:ERG 融合标志物的定量聚合酶链反应（qPCR）对尿液沉淀物中的 RNA 进行分析。
我们的融合标志物在尿液沉淀物中检测单个融合阳性癌细胞（VCaP）时，表现出非常高的技术特异性和敏感性，在至少 3000 个细胞存在的情况下。在临床分析中，前列腺癌阴性组（44 个样本中无一个）没有融合阳性样本，而确诊前列腺癌组中 16 个（34.8%）融合阳性样本。在三个 PCa 亚组中，融合发生率存在显著差异。在接受治疗前的癌症患者中，临床灵敏度提高至 45.4%。融合标志物在 11 名（18.2%）活检阴性患者中的 2 名中被检测到，提示潜在的假阴性活检。这项研究不是前瞻性的，样本量有限。
我们新的 TMPRSS2:ERG 融合标志物组提供了一种非常特异和敏感的基于尿液的 PCa 检测工具。这些标志物有可能用于诊断前列腺活检阴性的 PCa 患者。
