title: The detection of EpCAM(+) and EpCAM(-) circulating tumor cells.
abstract: 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.
authors.affiliation: Department of Medical Cell BioPhysics, University of Twente, Hallenweg 23, 7522NH Enschede, the Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: de Wit
authors.affiliation: Department of Medical Cell BioPhysics, University of Twente, Hallenweg 23, 7522NH Enschede, the Netherlands.
authors.forename: Guus
authors.initials: G
authors.lastname: van Dalum
authors.affiliation: Department of Medical Cell BioPhysics, University of Twente, Hallenweg 23, 7522NH Enschede, the Netherlands.
authors.forename: Aufried T M
authors.initials: AT
authors.lastname: Lenferink
authors.affiliation: VyCAP BV, Rademakerstraat 41, 7425PG Deventer, the Netherlands.
authors.forename: Arjan G J
authors.initials: AG
authors.lastname: Tibbe
authors.affiliation: Department of Pulmonology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
authors.forename: T Jeroen N
authors.initials: TJ
authors.lastname: Hiltermann
authors.affiliation: Department of Pulmonology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.affiliation: Laboratory of Organic Chemistry, University of Wageningen, Dreijenplein 8, 6703HB Wageningen, the Netherlands.
authors.forename: Cees J M
authors.initials: CJ
authors.lastname: van Rijn
authors.affiliation: Department of Medical Cell BioPhysics, University of Twente, Hallenweg 23, 7522NH Enschede, the Netherlands.
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007633:Keratins / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D007633:Keratins