Chen B T, Loberg R D, Neeley C K, O'Hara S M, Gross S, Doyle G, Dunn R L, Kalikin L M, Pienta K J
Department of Urology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Urology. 2005 Mar;65(3):616-21. doi: 10.1016/j.urology.2004.10.053.
To enumerate the amount of circulating tumor cells (CTCs) in patients with advanced prostate cancer and to investigate the relationship between these numbers, prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) expression, and clinical parameters.
Whole blood was collected in proprietary CellSave tubes. Mononuclear cell fractions were isolated using epithelial cell antibody-coated magnetic nanoparticles. On one half of each immunomagnetically enriched cell fraction, automated fluorescent microscopy was used to identify the epithelial tumor cells. From the remainder of each sample, RNA extraction, cDNA synthesis, and polymerase chain reaction amplification of PSA and PSM were performed.
Eighty-four patients with advanced prostate cancer submitted 130 samples for analysis. Intact CTCs were identified in 62% of samples; 83.3% of CTC-positive and 0% of CTC-negative samples were reverse transcriptase-polymerase chain reaction positive for PSA and PSM (P = 0.001). A significant positive correlation was found between the CTC number and PSA (r = 0.49), alkaline phosphatase (r = 0.47), and lactate dehydrogenase (r = 0.55) levels, and a significant negative correlation with hemoglobin (r = -0.35). The initial Gleason grade, prior therapy, current therapy, and type of metastasis (bone, soft tissue) did not correlate significantly with the CTC number.
The presence of intact CTCs and the expression of PSA and PSM demonstrated robust agreement. The tumor cell numbers reflected current disease status and correlated significantly with the clinical disease indicators of PSA, hemoglobin, and liver function tests. These findings warrant further investigation of the diagnostic and prognostic value of enumerating intact CTCs.
对晚期前列腺癌患者循环肿瘤细胞(CTC)数量进行计数,并研究这些数量与前列腺特异性抗原(PSA)、前列腺特异性膜抗原(PSM)表达以及临床参数之间的关系。
使用专用的CellSave管采集全血。采用上皮细胞抗体包被的磁性纳米颗粒分离单核细胞组分。在每个经免疫磁珠富集的细胞组分的一半样本上,利用自动荧光显微镜识别上皮肿瘤细胞。对每个样本的剩余部分进行RNA提取、cDNA合成以及PSA和PSM的聚合酶链反应扩增。
84例晚期前列腺癌患者提交了130份样本进行分析。在62%的样本中鉴定出完整的CTC;83.3%的CTC阳性样本和0%的CTC阴性样本的PSA和PSM逆转录聚合酶链反应呈阳性(P = 0.001)。发现CTC数量与PSA(r = 0.49)、碱性磷酸酶(r = 0.47)和乳酸脱氢酶(r = 0.55)水平呈显著正相关,与血红蛋白(r = -0.35)呈显著负相关。初始Gleason分级、既往治疗、当前治疗以及转移类型(骨、软组织)与CTC数量无显著相关性。
完整CTC的存在与PSA和PSM的表达表现出高度一致性。肿瘤细胞数量反映了当前疾病状态,并与PSA、血红蛋白和肝功能检查等临床疾病指标显著相关。这些发现值得进一步研究完整CTC计数的诊断和预后价值。