The detection of EpCAM+ and EpCAM– circulating tumor cells

• Published in: Scientific reports Vol. 5; no. 1; p. 12270
• Main Authors: Wit, Sanne de, Dalum, Guus van, Lenferink, Aufried T. M., Tibbe, Arjan G. J., Hiltermann, T. Jeroen N., Groen, Harry J. M., van Rijn, Cees J. M., Terstappen, Leon W. M. M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.07.2015; Nature Publishing Group
• Subjects: 14; 14/1; 14/34; 631/1647/245/2225; 631/67/1612/1350; 692/53/2421; Adult; Aged; Aged, 80 and over; Antibodies; Antigens, Neoplasm - metabolism; Biomarkers, Tumor; Biopsy; Case-Control Studies; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Cytokeratin; Efficiency; Epithelial Cell Adhesion Molecule; Female; Filtration; Flow Cytometry - methods; Follow-Up Studies; Humanities and Social Sciences; Humans; Kaplan-Meier Estimate; Keratins - metabolism; Labeling; Laboratorium voor Organische chemie; Laboratory for Organic Chemistry; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Male; Metastases; Metastasis; Middle Aged; multidisciplinary; Neoplasm Metastasis; Neoplastic Cells, Circulating - metabolism; Organic Chemistry; Organische Chemie; Patients; Prognosis; Science; Tumor cells; VLAG
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep12270

EpCAM expressing circulating tumor cells, detected by CellSearch, are predictive of short survival in several cancers and may serve as a liquid biopsy to guide therapy. Here we investigate the presence of EpCAM + CTC detected by CellSearch and EpCAM – CTC discarded by CellSearch, after EpCAM based enrichment. EpCAM – CTC were identified by filtration and fluorescent labelling. This approach was validated using different cell lines spiked into blood and evaluated on blood samples of 27 metastatic lung cancer patients. The majority of spiked EpCAM + cells could be detected with CellSearch, whereas most spiked cells with EpCAM low or EpCAM – expression were detected using filtration. Five or more CTC were detected in 15% of the patient samples, this increased to 41% when adding the CTC detected in the discarded blood. The number of patients with CTC and the number of CTC detected were doubled by the presence of EpCAM – CTC. In this pilot study, the presence of EpCAM + CTC was associated with poor outcome, whereas the EpCAM – CTC were not. This observation will need to be confirmed in larger studies and molecular characterization needs to be conducted to elucidate differences between EpCAM – and EpCAM + CTC.