Thomas Christian, Wiesner Christoph, Melchior Sebastian W, Schmidt Folke, Gillitzer Rolf, Thüroff Joachim W, Pfitzenmaier Jesco
Department of Urology, Johannes-Gutenberg University, Mainz, Germany.
BJU Int. 2009 Jul;104(1):29-34. doi: 10.1111/j.1464-410X.2008.08298.x. Epub 2008 Dec 22.
OBJECTIVE To evaluate the expression of urokinase-plasminogen-activator receptor (uPA-R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis. PATIENTS AND METHODS In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA-R expression was detected by dual-immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow-up was initiated to detect tumour relapse (defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL). RESULTS Overall, there was expression of 'CK + uPA-R' in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high-risk cancer (P = 0.005). The relative risk for CK + uPA-R expression in the BM was 3.1 times higher in high-risk than in low-risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA-R expression in BM or PB. The PSA-recurrence free survival was significantly lower in patients with CK + uPA-R-positive BM cells (P = 0.01). CONCLUSION In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high-risk disease. All patients with a later PSA relapse had had uPA-R expression in their DTC from the BM. DTC with uPA-R expression was an adverse prognostic factor for prostate cancer.
目的 评估根治性前列腺切除术（RP）前临床局限性前列腺癌患者骨髓（BM）和外周血（PB）中播散肿瘤细胞（DTC） uro激酶-纤溶酶原激活物受体（uPA-R）的表达，并评估其与病理变量及预后的相关性。 患者与方法 共前瞻性纳入52例患者（47例临床局限性癌症患者及5例良性前列腺增生（BPH）患者作为对照）。术前采集BM和PB样本。使用商业系统富集DTC，用细胞角蛋白（CK）8/18检测DTC，通过对DTC进行双重免疫染色检测uPA-R表达。将RP标本的最终病理结果与免疫染色结果进行比较。开始随访以检测肿瘤复发（定义为前列腺特异性抗原（PSA）水平≥0.2 ng/mL）。 结果 总体而言，60%的BM标本和19%的PB标本中有“CK + uPA-R”表达。该标志物在BM中的表达在Gleason评分不利的患者中增加最为显著（P = 0.004），其次是高危癌症患者（P = 0.005）。高危前列腺癌患者BM中CK + uPA-R表达的相对风险比低危患者高3.1倍。PB未检测到相关表达率。在对照组中，BM或PB中未发现患者有CK或uPA-R表达。CK + uPA-R阳性BM细胞的患者无PSA复发存活期显著更低（P = 0.01）。 结论 在这项初步研究中，前列腺癌患者BM中CK + uPAR表达的术前检测率随Gleason评分及高危疾病患者增加。所有后期PSA复发的患者其BM的DTC中均有uPA-R表达。uPA-R表达的DTC是前列腺癌的不良预后因素。
