title: Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response.
abstract: BACKGROUND
  Detection, isolation, and enumeration of circulating tumor cells (CTCs) from cancer patients has become an important modality in clinical management of patients with breast cancer. Although CellSearch, an epithelial cell adhesion molecule (EpCAM)-based method that is used to isolate epithelial CTCs, has gained prominence, its inability to detect mesenchymal CTCs from breast cancer patients raises concerns regarding its utility in clinical management.
  
  
  METHODS
  To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma tumors. In the present study, we tested the sensitivity and specificity of detecting CTCs from blood collected at a random time during therapy from each of 58 patients with metastatic breast cancer by use of 84-1 (a monoclonal antibody against CSV to detect epithelial/mesenchymal-transition CTCs) and CellSearch methods. Additionally, we tested the possibility of improving the sensitivity and specificity of detection by use of additional parameters including nuclear EpCAM localization and epithelial mesenchymal ratios.
  
  
  RESULTS
  CTC counts with CSV were significant (P = 0.0053) in differentiating populations responsive and nonresponsive to treatment compared with CTC counts with CellSearch (P = 0.0564). The specificity of CTC detection was found to be highest when the sum of CTC counts from the 2 methods was above a threshold of 8 CTCs/7.5 mL.
  
  
  CONCLUSIONS
  The sum of CTC counts from the CellSearch and CSV methods appears to provide new insights for assessment of therapeutic response and thus provides a new approach to personalized medicine in breast cancer patients.
authors.affiliation: Department of Pediatrics and.
authors.forename: Arun
authors.initials: A
authors.lastname: Satelli
authors.affiliation: Department of Pediatrics and.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Brownlee
authors.affiliation: Department of Pediatrics and.
authors.forename: Abhisek
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Qing H
authors.initials: QH
authors.lastname: Meng
authors.affiliation: Department of Pediatrics and The University of Texas Graduate School of Biomedical Sciences, Houston, TX. sli4@mdanderson.org.
authors.forename: Shulin
authors.initials: S
authors.lastname: Li
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000097:blood*; D002452:Cell Count; D002462:Cell Membrane / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000473:pathology*; D010865:Pilot Projects; D012189:Retrospective Studies; D016896:Treatment Outcome; D014746:Vimentin / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D014746:Vimentin