Abstract
Cancer metastasis occurs when cells shed from a primary or metastatic tumor, enter the circulation, and begin to grow in distant locations of the body. With current techniques it is possible to measure the presence of a few circulating tumor cells (CTC) in a blood sample. Detection of even the presence of a very small number (one or more) of these CTC in a 7.5 mL blood sample with the CellSearch system is associated with a significant decrease in survival of patients with metastatic carcinomas. The techniques and definitions used for the detection and enumeration of CTC with the CellSearch system were validated in series of preclinical and prospective multicenter studies. After enumeration of the CTC, the cells can be isolated from the cartridge for the purpose of downstream single-cell analysis. In this chapter, we will describe in detail the sample acquisition, sample preparation, data acquisition, and assignment of CTC used in the CellSearch system.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Terstappen LWMM, Rao C, Gross S, Kotelnikov V, Racila E, Uhr J, Weiss A (1998) Enumeration of epithelial derived tumor cells in peripheral blood. Vox Sanguinis 74:269–274
Racila E, Euhus D, Weiss AJ, Rao C, McConnell J, Terstappen LWMM, Uhr JW (1998) Detection and characterization of carcinoma cells in the blood. PNAS 95:4589–4594
Terstappen LWMM, Rao C, Gross S, Weiss A (2000) Peripheral blood tumor cell load reflects the clinical activity of the disease in patients with carcinoma of the breast. Int J Oncol 17:573–578
Moreno JG, O’Hara SM, Gross S, Doyle G, Fritsche H, Gomella LG, Terstappen LWMM (2001) Changes in circulating carcinoma cells in metastatic prostate cancer patients correlates with disease status. Urology 58:386–392
Hayes DF, Walker TM, Singh B, Vitetta ES, Uhr JW, Gross S, Rao C, Doyle GV, Terstappen LWMM (2002) Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int J Oncol 21:1111–1118
Liberi PA, Rao CG, Terstappen LWMM (2001) Optimization of ferrofluids and protocols for the enrichment of breast tumor cells in blood. J Magn Magn Mater 225:301–307
Kagan M, Howard D, Bendele T, Mayes J, Silvia J, Repollet M, Doyle J, Allard J, Tu N, Bui T, Russell T, Rao C, Hermann M, Rutner H, Terstappen LWMM (2002) A sample preparation and analysis system for identification of circulating tumor cells. J Clin Ligand Assay 25:104
Rao CG, Chianese D, Doyle GV, Miller MC, Russell T, Sanders RA, Terstappen LWMM (2005) Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and primary and metastatic tumors. Int J Oncol 27:49–58
Larson CJ, Moreno JG, Pienta KJ, Gross S, Repollet M, O’Hara SM, Russell T, Terstappen LWMM (2004) Apoptosis of circulating tumor cells in prostate cancer patients. Cytometry 62A:46–53
Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe A, Uhr JW, Terstappen LWMM (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with non-malignant diseases. Clin Can Res 10:6897–6904
Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Rueben JM, Doyle G, Allard WJ, Terstappen LWMM, Hayes DF (2004) Circulating tumor cells, disease progression and survival in metastatic breast cancer. NEJM 351:781–791
Cohen SJ, Punt CJA, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Desch CE, Miller MC, Doyle GV, Tissing H, Terstappen LWMM, Meropol NJ (2008) The relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26:3213–3221
DeBono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LWWM, Pienta KJ, Raghavan D (2008) Circulating tumor cells (CTC) predict survival benefit from treatment in metastatic castration resistant prostate cancer (CRPC). Clin Can Res 14:6302–6309
Miller MC, Doyle GV, Terstappen LWMM (2009) Significance of circulating tumor cells detected by the CellSearch® system in patients with metastatic breast colorectal and prostate cancer. J Oncol 1–8, Article ID 617421
Coumans F, Doggen CJM, Attard G, de Bono JS, Terstappen LWMM (2010) All circulating EpCAM + CD45-CK+ but not EpCAM + CD45 + CK+ objects predict overall survival in castration-resistant prostate cancer. Ann Oncol 21:1851–1857
Tibbe AGJ, de Grooth BG, Greve J, Dolan GJ, Rao C, Terstappen LWMM (2002) Magnetic field design for selecting and aligning immunomagnetic labeled cells. Cytometry 47:163–172
Tibbe AGJ, Miller C, Terstappen LWMM (2007) Statistical considerations for enumeration of circulating tumor cells. Cytometry A 71A:154–162
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Coumans, F., Terstappen, L. (2015). Detection and Characterization of Circulating Tumor Cells by the CellSearch Approach. In: Kroneis, T. (eds) Whole Genome Amplification. Methods in Molecular Biology, vol 1347. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2990-0_18
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2990-0_18
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2989-4
Online ISBN: 978-1-4939-2990-0
eBook Packages: Springer Protocols