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 |
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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. |
doi_str_mv | 10.1373/clinchem.2014.228122 |
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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.</description><identifier>ISSN: 0009-9147</identifier><identifier>EISSN: 1530-8561</identifier><identifier>DOI: 10.1373/clinchem.2014.228122</identifier><identifier>PMID: 25336717</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>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</subject><ispartof>Clinical chemistry (Baltimore, Md.), 2015-01, Vol.61 (1), p.259-266</ispartof><rights>2014 American Association for Clinical Chemistry.</rights><rights>Copyright American Association for Clinical Chemistry Jan 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-352298fe1a80449620147570d13d42b7cad03e413fe8311ab570e59d5c17db693</citedby><cites>FETCH-LOGICAL-c381t-352298fe1a80449620147570d13d42b7cad03e413fe8311ab570e59d5c17db693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25336717$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Satelli, Arun</creatorcontrib><creatorcontrib>Brownlee, Zachary</creatorcontrib><creatorcontrib>Mitra, Abhisek</creatorcontrib><creatorcontrib>Meng, Qing H</creatorcontrib><creatorcontrib>Li, Shulin</creatorcontrib><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</title><title>Clinical chemistry (Baltimore, Md.)</title><addtitle>Clin Chem</addtitle><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.</description><subject>Adhesion</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antigens, Neoplasm - blood</subject><subject>Biomarkers, Tumor - blood</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - blood</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Adhesion Molecules - blood</subject><subject>Cell Count</subject><subject>Cell Membrane - metabolism</subject><subject>Epithelial Cell Adhesion Molecule</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Female</subject><subject>Humans</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Monitoring methods</subject><subject>Neoplasm Metastasis</subject><subject>Neoplastic Cells, Circulating - 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Academic</collection><jtitle>Clinical chemistry (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Satelli, Arun</au><au>Brownlee, Zachary</au><au>Mitra, Abhisek</au><au>Meng, Qing H</au><au>Li, Shulin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response</atitle><jtitle>Clinical chemistry (Baltimore, Md.)</jtitle><addtitle>Clin Chem</addtitle><date>2015-01</date><risdate>2015</risdate><volume>61</volume><issue>1</issue><spage>259</spage><epage>266</epage><pages>259-266</pages><issn>0009-9147</issn><eissn>1530-8561</eissn><abstract>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.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>25336717</pmid><doi>10.1373/clinchem.2014.228122</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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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