5 u/ U; T' J" K% ]- N循环肿瘤细胞检测中用到几个具体指标，其中之一是上皮细胞粘附分子（EpCAM），这类粘附分子在正常血细胞中不存在。其他指标还包括细胞角蛋白和CD45，但任何白血细胞意外含有微量EpCAM和细胞角蛋白，都可能会被错误地计算成为循环肿瘤细胞。+ g! N, G$ A$ _/ f, x# n7 i
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研究组通过使用一种改进的CellSearch分析仪改进循环肿瘤细胞检测。然而，根据医生Coumans表示，只有这样才能检测样品中99％的CTC。但这种方法需要使用额外的技术，最好是使用新鲜血液。博士Coumans的研究是欧洲研究项目的一部分，他预计这一方法将可能进入临床测试阶段。（生物谷：Bioon.com）" @0 [. q7 _1 V
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6 B2 b, R, o" M2 H9 Tdoi:10.1158/1078-0432.CCR-12-1585: i' H. R; I3 L1 B, h% `
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PMID: # L7 ?+ A4 M) r2 s" x# l2 Q* w; d6 e - X* v O, |9 \. W' T) \+ V/ xChallenges in the Enumeration and Phenotyping of CTC9 |7 l* F. B# f T$ Z$ \& ~
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Frank A.W. Coumans, Sjoerd T. Ligthart, Jonathan W. Uhr, and Leon W.M.M. Terstappen1 ?# W! w w( }6 V8 W, ~& V. e
* h* v2 R9 q8 |2 R' x% ^2 ]9 Y; @Purpose: Presence of circulating tumor cells (CTC) in metastatic carcinoma is associated with poor survival. Phenotyping and genotyping of CTC may permit “real-time” treatment decisions, provided CTCs are available for examination. Here, we investigate what is needed to detect CTC in all patients.! U6 f Z; _6 d% {" r9 G. X. \
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Experimental Design: CTCs enumerated in 7.5 mL of blood together with survival from 836 patients with metastatic breast, colorectal, and prostate cancer were used to predict the CTC concentration in the 42% of these patients in whom no CTCs were found and to establish the relation of concentration of CTCs with survival. Influence of different CTC definitions were investigated by automated cell recognition and a flow cytometric assay without an enrichment or permeabilization step. : f# p$ A1 D1 E/ Y" k/ r4 W& ~7 T3 l- [/ o t9 u& N5 Y* h7 c
Results: A log-logistic regression of the log of CTC yielded a good fit to the CTC frequency distribution. Extrapolation of the blood volume to 5 L predicted that 99% of patients had at least one CTC before therapy initiation. Survival of patients with EpCAM+, cytokeratin+, CD45? nucleated CTCs is reduced by 6.6 months for each 10-fold CTC increase. Using flow cytometry, the potential three-fold recovery improvement is not sufficient to detect CTC in all patients in 7.5 mL of blood. ' f$ b) t: H0 d8 A( D, d9 _1 ~" j+ c* b" C4 I; x0 W/ B
Conclusions: EpCAM+, cytokeratin+, CD45? nucleated CTCs are present in all patients with metastatic breast, prostate, and colorectal cancer and their frequency is proportional to survival. To serve as a liquid biopsy for the majority of patients, a substantial improvement of CTC yield is needed, which can only be achieved by a dramatic increase in sample volume.