Enrichment, Isolation and Molecular Characterization of EpCAM-Negative Circulating Tumor Cells

  • Rita Lampignano
  • Helen Schneck
  • Martin Neumann
  • Tanja Fehm
  • Hans NeubauerEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 994)


The presence of EpCAM-positive circulating tumor cells (CTCs) in the peripheral blood is associated with poor clinical outcomes in breast, colorectal and prostate cancer, as well as the prognosis of other tumor types. In addition, recent studies have suggested that the presence of CTCs undergoing epithelial-to-mesenchymal transition and, as such, may exhibit reduced or no expression of epithelial proteins e.g. EpCAM, might be related to disease progression in metastatic breast cancer (MBC) patients. Analyzing the neoplastic nature of this EpCAM-low/negative (EpCAM-neg) subpopulation remains an open issue as the current standard detection methods for CTCs are not efficient at identifying this subpopulation of cells. The possible association of EpCAM-neg CTCs with EpCAM-positive (EpCAM-pos) CTCs and role in the clinicopathological features and prognosis of MBC patients has still to be demonstrated. Several technologies have been developed and are currently being tested for the identification and the downstream analyses of EpCAM-pos CTCs. These technologies can be adapted and implemented into workflows to isolate and investigate EpCAM-neg cells to understand their biology and clinical relevance. This chapter will endeavour to explain the rationale behind the identification and analyses of all CTC subgroups, as well as to review the current strategies employed to enrich, isolate and characterize EpCAM-negative CTCs. Finally, the latest findings in the field will briefly be discussed with regard to their clinical relevance.


Single cell isolation Molecular analysis EPCAM-negative 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Rita Lampignano
    • 1
  • Helen Schneck
    • 1
  • Martin Neumann
    • 1
  • Tanja Fehm
    • 1
  • Hans Neubauer
    • 2
    Email author
  1. 1.Department of Obstetrics and GynecologyUniversity Hospital and Medical Faculty of the Heinrich-Heine University DuesseldorfDuesseldorfGermany
  2. 2.Forschungslabore der Frauenklinik desUniversitätsklinikums Düsseldorf, Life Science CenterDüsseldorfGermany

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