Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer
Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer
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DOI：
10.1158/1078-0432.ccr-06-2701
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发表时间：
2007-04-01
影响因子：
11.5
通讯作者：
Scher, Howard I.
中科院分区：
文献类型：
--
作者：
Shaffer, David R.;Leversha, Margaret A.;Scher, Howard I.
目的：为了更好地将靶向治疗引导至具有表达靶标的肿瘤的患者，迫切需要基于血液的测定，其在真实的时间以最小的患者不适在一致的基础上提供表达信息。我们的目的是使用免疫磁性捕获技术分离和分析循环肿瘤细胞（CTC）从小体积的晚期前列腺癌患者的外周血。实验设计：血液收集63例转移性前列腺癌患者。通过CellSearch系统分离CTC，该系统使用上皮细胞粘附标志物的抗体和免疫磁性捕获。CTC定义为细胞角蛋白阳性和CD45阴性的有核细胞。捕获的细胞进行了分析，免疫荧光，巴氏染色，荧光原位hybridization.Results：大多数患者（65%）有5个或更多的CTC每7.5 mL的血液样本。实验室之间的细胞计数一致（c = 0.99），并且在处理前储存72或96 h内无显著变化（c = 0.99）。它们作为前列腺癌细胞的身份通过常规细胞学分析确认。分子分析，包括分析表皮生长因子受体（EGFR）的表达，染色体倍性，雄激素受体（AR）基因扩增，是可能的所有前列腺癌患者>= 5 CTCs.Conclusions：癌症相关的改变在DNA和蛋白质水平的分析，从CTC是可行的，在医院为基础的临床实验室。在EGFR和AR中观察到的改变表明该方法可能在临床决策中发挥作用。
Purpose: To better direct targeted therapies to the patients with tumors that express the target, there is an urgent need for blood-based assays that provide expression information on a consistent basis in real time with minimal patient discomfort. We aimed to use immunomagnetic-capture technology to isolate and analyze circulating tumor cells (CTC) from small volumes of peripheral blood of patients with advanced prostate cancer.Experimental Design: Blood was collected from 63 patients with metastatic prostate cancer. CTCs were isolated by the CellSearch system, which uses antibodies to epithelial cell adhesion marker and immunomagnetic capture. CTCs were defined as nucleated cells positive for cytokeratins and negative for CD45. Captured cells were analyzed by immunofluorescence, Papanicolau staining, and fluorescence in situ hybridization.Results: Most patients (65%) had 5 or more CTCs per 7.5 mL blood sample. Cell counts were consistent between laboratories (c = 0.99) and did not change significantly over 72 or 96 h of storage before processing (c = 0.99). Their identity as prostate cancer cells was confirmed by conventional cytologic analysis. Molecular profiling, including analysis of epidermal growth factor receptor (EGFR) expression, chromosome ploidy, and androgen receptor (AR) gene amplification, was possible for all prostate cancer patients with >= 5 CTCs.Conclusions: The analysis of cancer-related alterations at the DNA and protein level from CTCs is feasible in a hospital-based clinical laboratory. The alterations observed in EGFR and AR suggest that the methodology may have a role in clinical decision making.