A Comprehensive Molecular Analysis of in Vivo Isolated EpCAM-Positive Circulating Tumor Cells in Breast Cancer
Abstract Background Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa). Methods In vivo isolated CTCs from 42 patients with early and 23 patients wit...
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| Veröffentlicht in: | Clinical chemistry (Baltimore, Md.) Md.), 2021-10, Vol.67 (10), p.1395-1405 |
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| creator | Strati, Areti Zavridou, Martha Kallergi, Galatea Politaki, Eleni Kuske, Andra Gorges, Tobias M Riethdorf, Sabine Joosse, Simon A Koch, Claudia Bohnen, Anna-Lena Mueller, Volkmar Koutsodontis, George Kontopodis, Emmanouil Poulakaki, Nikiforita Psyrri, Amanda Mavroudis, Dimitris Georgoulias, Vasilis Pantel, Klaus Lianidou, Evi S |
| description | Abstract
Background
Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa).
Methods
In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining.
Results
All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection.
Conclusions
In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs. |
| doi_str_mv | 10.1093/clinchem/hvab099 |
| format | Article |
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Background
Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa).
Methods
In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining.
Results
All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection.
Conclusions
In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs.</description><identifier>ISSN: 0009-9147</identifier><identifier>EISSN: 1530-8561</identifier><identifier>DOI: 10.1093/clinchem/hvab099</identifier><identifier>PMID: 34322698</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Analysis ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biopsy ; Breast cancer ; Breast Neoplasms - pathology ; Cancer cells ; CD44 antigen ; Creatine ; Creatine kinase ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Epithelial Cell Adhesion Molecule - genetics ; ErbB-2 protein ; ESR1 protein ; Female ; Gene expression ; Gene mutations ; Genetic aspects ; Humans ; Identification and classification ; In vivo methods and tests ; Kinases ; Liquid Biopsy ; Metastases ; Methods ; Methylation ; Mutation ; Neoplastic Cells, Circulating - pathology ; Patients ; Staining ; Therapy ; Tumor cells ; Tumors ; Vascular endothelial growth factor</subject><ispartof>Clinical chemistry (Baltimore, Md.), 2021-10, Vol.67 (10), p.1395-1405</ispartof><rights>American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2021</rights><rights>American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2021 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-4c513ddf74ff777a78791db3c13c081472e0f67d1f1bbe574f9ed063a9377c1f3</citedby><cites>FETCH-LOGICAL-c439t-4c513ddf74ff777a78791db3c13c081472e0f67d1f1bbe574f9ed063a9377c1f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34322698$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strati, Areti</creatorcontrib><creatorcontrib>Zavridou, Martha</creatorcontrib><creatorcontrib>Kallergi, Galatea</creatorcontrib><creatorcontrib>Politaki, Eleni</creatorcontrib><creatorcontrib>Kuske, Andra</creatorcontrib><creatorcontrib>Gorges, Tobias M</creatorcontrib><creatorcontrib>Riethdorf, Sabine</creatorcontrib><creatorcontrib>Joosse, Simon A</creatorcontrib><creatorcontrib>Koch, Claudia</creatorcontrib><creatorcontrib>Bohnen, Anna-Lena</creatorcontrib><creatorcontrib>Mueller, Volkmar</creatorcontrib><creatorcontrib>Koutsodontis, George</creatorcontrib><creatorcontrib>Kontopodis, Emmanouil</creatorcontrib><creatorcontrib>Poulakaki, Nikiforita</creatorcontrib><creatorcontrib>Psyrri, Amanda</creatorcontrib><creatorcontrib>Mavroudis, Dimitris</creatorcontrib><creatorcontrib>Georgoulias, Vasilis</creatorcontrib><creatorcontrib>Pantel, Klaus</creatorcontrib><creatorcontrib>Lianidou, Evi S</creatorcontrib><title>A Comprehensive Molecular Analysis of in Vivo Isolated EpCAM-Positive Circulating Tumor Cells in Breast Cancer</title><title>Clinical chemistry (Baltimore, Md.)</title><addtitle>Clin Chem</addtitle><description>Abstract
Background
Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa).
Methods
In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining.
Results
All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection.
Conclusions
In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs.</description><subject>Analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biopsy</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer cells</subject><subject>CD44 antigen</subject><subject>Creatine</subject><subject>Creatine kinase</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epithelial Cell Adhesion Molecule - genetics</subject><subject>ErbB-2 protein</subject><subject>ESR1 protein</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>In vivo methods and tests</subject><subject>Kinases</subject><subject>Liquid Biopsy</subject><subject>Metastases</subject><subject>Methods</subject><subject>Methylation</subject><subject>Mutation</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Patients</subject><subject>Staining</subject><subject>Therapy</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Vascular endothelial growth 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Andra</creator><creator>Gorges, Tobias M</creator><creator>Riethdorf, Sabine</creator><creator>Joosse, Simon A</creator><creator>Koch, Claudia</creator><creator>Bohnen, Anna-Lena</creator><creator>Mueller, Volkmar</creator><creator>Koutsodontis, George</creator><creator>Kontopodis, Emmanouil</creator><creator>Poulakaki, Nikiforita</creator><creator>Psyrri, Amanda</creator><creator>Mavroudis, Dimitris</creator><creator>Georgoulias, Vasilis</creator><creator>Pantel, Klaus</creator><creator>Lianidou, Evi S</creator><general>Oxford University 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Comprehensive Molecular Analysis of in Vivo Isolated EpCAM-Positive Circulating Tumor Cells in Breast Cancer</title><author>Strati, Areti ; Zavridou, Martha ; Kallergi, Galatea ; Politaki, Eleni ; Kuske, Andra ; Gorges, Tobias M ; Riethdorf, Sabine ; Joosse, Simon A ; Koch, Claudia ; Bohnen, Anna-Lena ; Mueller, Volkmar ; Koutsodontis, George ; Kontopodis, Emmanouil ; Poulakaki, Nikiforita ; Psyrri, Amanda ; Mavroudis, Dimitris ; Georgoulias, Vasilis ; Pantel, Klaus ; Lianidou, Evi S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-4c513ddf74ff777a78791db3c13c081472e0f67d1f1bbe574f9ed063a9377c1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biopsy</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer cells</topic><topic>CD44 antigen</topic><topic>Creatine</topic><topic>Creatine kinase</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Epithelial Cell Adhesion Molecule - genetics</topic><topic>ErbB-2 protein</topic><topic>ESR1 protein</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>In vivo methods and tests</topic><topic>Kinases</topic><topic>Liquid Biopsy</topic><topic>Metastases</topic><topic>Methods</topic><topic>Methylation</topic><topic>Mutation</topic><topic>Neoplastic Cells, Circulating - pathology</topic><topic>Patients</topic><topic>Staining</topic><topic>Therapy</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strati, 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Tumor Cells in Breast Cancer</atitle><jtitle>Clinical chemistry (Baltimore, Md.)</jtitle><addtitle>Clin Chem</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>67</volume><issue>10</issue><spage>1395</spage><epage>1405</epage><pages>1395-1405</pages><issn>0009-9147</issn><eissn>1530-8561</eissn><abstract>Abstract
Background
Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa).
Methods
In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining.
Results
All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection.
Conclusions
In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>34322698</pmid><doi>10.1093/clinchem/hvab099</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0009-9147 |
| ispartof | Clinical chemistry (Baltimore, Md.), 2021-10, Vol.67 (10), p.1395-1405 |
| issn | 0009-9147 1530-8561 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2556384795 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE |
| subjects | Analysis Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Biopsy Breast cancer Breast Neoplasms - pathology Cancer cells CD44 antigen Creatine Creatine kinase Deoxyribonucleic acid DNA DNA Methylation Epithelial Cell Adhesion Molecule - genetics ErbB-2 protein ESR1 protein Female Gene expression Gene mutations Genetic aspects Humans Identification and classification In vivo methods and tests Kinases Liquid Biopsy Metastases Methods Methylation Mutation Neoplastic Cells, Circulating - pathology Patients Staining Therapy Tumor cells Tumors Vascular endothelial growth factor |
| title | A Comprehensive Molecular Analysis of in Vivo Isolated EpCAM-Positive Circulating Tumor Cells in Breast Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T14%3A27%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Comprehensive%20Molecular%20Analysis%20of%20in%20Vivo%20Isolated%20EpCAM-Positive%20Circulating%20Tumor%20Cells%20in%20Breast%20Cancer&rft.jtitle=Clinical%20chemistry%20(Baltimore,%20Md.)&rft.au=Strati,%20Areti&rft.date=2021-10-01&rft.volume=67&rft.issue=10&rft.spage=1395&rft.epage=1405&rft.pages=1395-1405&rft.issn=0009-9147&rft.eissn=1530-8561&rft_id=info:doi/10.1093/clinchem/hvab099&rft_dat=%3Cgale_proqu%3EA688155505%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2580659489&rft_id=info:pmid/34322698&rft_galeid=A688155505&rft_oup_id=10.1093/clinchem/hvab099&rfr_iscdi=true |