Zhao Lina, Li Pengfei, Li Fude, Yang Yongkun, Liu Na, Cai Li
Department of Medicine, the Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
J Cancer Res Ther. 2013 Jan-Mar;9(1):29-37. doi: 10.4103/0973-1482.110353.
In this study, we detected epithelial circulating tumor cells (CTCs) that expressed cytokeratins and potential circulating tumor cells (pCTCs) that had lost expression of cytokeratins in metastatic breast cancer (MBC) patients. The aim of the study was to evaluate the prognostic significance of these two kinds of CTCs in MBC patients.
We detected CTCs and pCTCs from 66 MBC patients using MACS immunomagnetic enrichment technology combined with immunocytochemistry (ICC). A cutoff score of 5 CTCs (or pCTCs) was set as a benchmark for prognosis in patients. Progression free survival (PFS) was calculated and analyzed during the following 24 months.
We evaluated the sensitivity of this method and recovery rates of the CTCs by spiking experiments. The loss number of tumor cells by our method was 0-15. The population with fewer than 5 CTCs showed significantly higher PFS than the group with 5 or more CTCs. The difference in PFS between the patients with 5 or more pCTCs and those with fewer than 5 pCTCs was statistically significant. The presence of these pCTCs more accurately predicted poor prognosis than the CTCs that express cytokeratins.
There is a subset of CTCs that lose epithelial markers such as pCTCs. Due to the heterogeneity of the expression of epithelial antigens in CTCs, different subtypes of CTCs exist. Independently of CTCs, the groups of patients with pCTCs had poorer prognoses.
在本研究中，我们检测了转移性乳腺癌（MBC）患者中表达细胞角蛋白的上皮循环肿瘤细胞（CTC）以及失去细胞角蛋白表达的潜在循环肿瘤细胞（pCTC）。本研究的目的是评估这两种CTC在MBC患者中的预后意义。
我们采用MACS免疫磁珠富集技术结合免疫细胞化学（ICC），对66例MBC患者的CTC和pCTC进行检测。将5个CTC（或pCTC）的截断值作为患者预后的基准。计算并分析接下来24个月内的无进展生存期（PFS）。
我们通过加标实验评估了该方法的敏感性以及CTC的回收率。我们的方法导致肿瘤细胞损失数量为0 - 15个。CTC少于5个的人群的PFS显著高于CTC为5个或更多的组。5个或更多pCTC的患者与少于5个pCTC的患者之间的PFS差异具有统计学意义。与表达细胞角蛋白的CTC相比，这些pCTC的存在更准确地预测了不良预后。
存在一部分失去上皮标志物的CTC亚群，如pCTC。由于CTC中上皮抗原表达的异质性，存在不同亚型的CTC。独立于CTC，pCTC患者组的预后较差。
