Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence.
Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence.
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DOI：
10.1158/1078-0432.ccr-08-1754
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发表时间：
2009-01-15
期刊：
影响因子：
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通讯作者：
Vessella RL
中科院分区：
文献类型：
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作者：
Morgan TM;Lange PH;Porter MP;Lin DW;Ellis WJ;Gallaher IS;Vessella RL
患有明显局限性前列腺癌的男性通常在根治性前列腺切除术（RP）后数年复发。我们试图确定从RP后患者的骨髓（BM）中鉴定出的上皮样细胞（通常称为播散性肿瘤细胞，DTC）是否与生化复发（BR）相关。我们从RP前的569名男性和PSA<2.5 ng/ml的34名健康男性中获得BM抽吸物，以建立对照组。此外，建立了一个由98例RP后无疾病证据（NED）患者组成的分析队列，以评估DTC与BR之间的关系。通过用CD 45和CD 61抗体（阴性选择）进行磁珠富集，然后用人上皮抗原抗体（阳性选择）进行检测，并用FITC标记的抗BerEP 4抗体进行确认，从而检测BM中的上皮细胞。在RP之前，72%（408/569）的患者存在DTC。与病理分期、Gleason分级、术前PSA无相关性。34例对照中有3例（8.8%）存在DTC。在RP后NED患者中，56/98（57%）存在DTC。在RP后12/14（86%）NED患者中检测到DTC，随后发生BR。NED患者中DTC的存在是复发的独立预测因素（HR 6.9，CI 1.03-45.9）。大约70%接受RP的男性在手术前在BM中检测到DTC，这表明这些细胞在疾病早期逃逸。虽然术前DTC状态与病理危险因素无关，但NED患者RP后DTC的持续性是复发的独立预测因素。
Men with apparently localized prostate cancer often relapse years after radical prostatectomy (RP). We sought to determine if epithelial-like cells identified from bone marrow (BM) in patients after RP (commonly called disseminated tumor cells, DTC) were associated with biochemical recurrence (BR). We obtained BM aspirates from 569 men prior to RP and from 34 healthy men with PSA<2.5 ng/ml to establish a comparison group. Additionally, an analytic cohort consisting of 98 patients after RP with no evidence of disease (NED) was established to evaluate the relationship between DTC and BR. Epithelial cells in the BM were detected by magnetic bead enrichment with antibodies to CD45 and CD61 (negative selection) followed by antibodies to human epithelial antigen (positive selection) and confirmation with FITC-labeled anti-BerEP4 antibody. DTC were present in 72% (408/569) of patients prior to RP. There was no correlation with pathologic stage, Gleason grade, or pre-operative PSA. Three of 34 controls (8.8%) had DTC present. In patients NED post-RP, DTC were present in 56/98 (57%). DTC were detected in 12/14 (86%) NED patients post-RP who subsequently suffered BR. Presence of DTC in NED patients was an independent predictor of recurrence (HR 6.9, CI 1.03–45.9). Approximately 70% of men undergoing RP had DTC detected in their BM prior to surgery, suggesting that these cells escape early in the disease. Though pre-operative DTC status does not correlate with pathologic risk factors, persistence of DTC after RP in NED patients was an independent predictor of recurrence.