Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: correlation with disease stage
Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: correlation with disease stage
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DOI：
10.1023/b:brea.0000036897.92513.72
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发表时间：
2004-08-01
影响因子：
3.8
通讯作者：
Marks, A
中科院分区：
文献类型：
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作者：
Kahn, HJ;Presta, A;Marks, A
乳腺癌患者外周血中循环肿瘤细胞（CTC）的生物学和临床意义尚不清楚。为了研究这个问题，我们使用直接可视化分析将CTC的数量与疾病阶段和进展相关联。通过过滤从有核细胞级分中富集CTC，并在用抗细胞角蛋白8（CK 8）抗体CAM 5.2免疫染色后目视计数。在混合实验中，我们实现了每5 ml血液5个MCF 7细胞或5 x 10（7）个外周血白细胞（PBL）的检测限。我们在任何对照受试者中均未检测到CTC（0/20）。在131例乳腺癌患者中，我们发现远处转移患者CTC的发生率为36/51（71%），高于淋巴结阳性患者17/36（47%）（p = 0.026）或淋巴结阴性患者17/44（39%）（p = 0.001）。通过随时间重复采样，在个体患者中观察到的CTC最高数量的分布范围为1 - 700/5 ml血液，在远处转移患者中有更高数量的趋势。与以前的研究相同的特异性相比，基于在对照中类似的CTC的缺乏，我们报告了在淋巴结阴性和淋巴结阳性患者中CTC的更高发生率，这表明通过我们的方法更频繁地检测CTC。这种较高的发病率部分是由于我们的研究人群随着时间的推移而重复抽样。我们的研究结果支持CTC可以在外周血中检测和计数的概念，并且这种微创检测作为疾病进展的潜在预后指标和标志物值得进一步评估。
The biological and clinical significance of circulating tumor cells (CTC) in the peripheral blood of breast cancer patients is not known. To study this question, we used a direct visualization assay to correlate the number of CTC with disease stage and progression. The CTC were enriched from the nucleated cell fraction by filtration and enumerated visually following immunostaining with anti-cytokeratin 8 (CK8) antibody CAM 5.2. In mixing experiments, we achieved a limit of detection of 5 MCF7 cells per 5 ml of blood or 5 x 10(7) peripheral blood leukocytes (PBL). We did not detect CTC in any control subjects (0/20). In 131 breast cancer patients, we found a higher incidence of CTC in patients with distant metastatic 36/51 (71%) than those with node-positive 17/36 (47%) (p = 0.026), or node-negative 17/44 (39%) (p = 0.001) disease. The distribution of the highest numbers of CTC observed in individual patients by repeated sampling over time ranged from 1 to 700 per 5 ml of blood with a trend toward higher numbers in those with distant metastases. In comparison with previous studies of equal specificity, based on a similar absence of CTC in controls, we report a higher incidence of CTC in node-negative and node-positive patients, suggesting a more frequent detection of CTC by our approach. This higher incidence was achieved, in part, by repeated sampling of our study population over time. Our results support the concept that CTC can be detected and enumerated in peripheral blood and that this minimally invasive assay merits further evaluation as a potential prognostic indicator and marker of disease progression.