Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response

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,...

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Veröffentlicht in:Clinical chemistry (Baltimore, Md.) Md.), 2015-01, Vol.61 (1), p.259-266
Hauptverfasser: Satelli, Arun, Brownlee, Zachary, Mitra, Abhisek, Meng, Qing H, Li, Shulin
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container_title Clinical chemistry (Baltimore, Md.)
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creator Satelli, Arun
Brownlee, Zachary
Mitra, Abhisek
Meng, Qing H
Li, Shulin
description 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. 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. 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. 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.
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subjects Adhesion
Antibodies, Monoclonal - immunology
Antigens, Neoplasm - blood
Biomarkers, Tumor - blood
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Adhesion Molecules - blood
Cell Count
Cell Membrane - metabolism
Epithelial Cell Adhesion Molecule
Epithelial-Mesenchymal Transition - drug effects
Female
Humans
Medical research
Metastasis
Methods
Monitoring methods
Neoplasm Metastasis
Neoplastic Cells, Circulating - drug effects
Neoplastic Cells, Circulating - pathology
Patients
Pilot Projects
Retrospective Studies
Sarcoma
Studies
Treatment Outcome
Vimentin - immunology
Vimentin - metabolism
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
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