Detection and characterization of carcinoma cells in the blood

Detection and characterization of carcinoma cells in the blood
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DOI:
10.1073/pnas.95.8.4589
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发表时间:
1998-04-14
影响因子:
11.1
通讯作者:
Uhr, JW
Uhr, JW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Racila, E;Euhus, D;Uhr, JW

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已开发出一种将免疫磁性富集与多参数流式细胞术和免疫细胞化学分析相结合的高灵敏度检测方法,用于检测、计数和表征血液中的癌细胞。该测定可以检测1 ml血液中的一个上皮细胞或更少。用流式细胞术检测了30例乳腺癌患者、3例前列腺癌患者和13例对照者的外周血(10-20 ml)中循环上皮细胞(定义为核酸(+)、CD 45(-)和细胞角蛋白(+))的存在。在正常对照组和癌症患者(包括17例器官局限性疾病患者)之间,发现循环上皮细胞数量存在高度显着差异。为了确定癌症患者中的循环上皮细胞是否为肿瘤细胞,在免疫磁性富集后制备细胞离心涂片并进行分析。乳腺癌患者的上皮细胞通常用抗细胞角蛋白的mAb染色,5种中有3种用粘蛋白-1染色。相反,在正常对照的血液中没有观察到针对这些抗原染色的细胞。染色细胞的形态与肿瘤细胞的形态一致。在8例随访1-10个月的乳腺癌患者中,血液中肿瘤细胞水平的变化与化疗治疗和临床状态之间存在良好的相关性。本试验可能有助于早期发现,监测疾病,并在统计。
A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 mi) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid(+), CD45(-), and cytokeratin(+). Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.