Circulating Tumor Cells (CTCs) Detected by Triple-Marker EpCAM, CK19, and hMAM RT-PCR and Their Relation to Clinical Outcome in Metastatic Breast Cancer Patients

In order to investigate the prognostic value of circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC), the blood cells from 98 MBC patients and 60 controls were evaluated by RT-PCR to detect the presence of markers EpCAM , CK19 , and hMAM . Peripheral blood was obtained from...

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Veröffentlicht in:Cell biochemistry and biophysics 2013-03, Vol.65 (2), p.263-273
Hauptverfasser: Zhao, Shu, Yang, Huike, Zhang, Minghui, Zhang, Dekai, Liu, Yupeng, Liu, Yan, Song, Ying, Zhang, Xiaosan, Li, Hongbin, Ma, Wenjie, Zhang, Qingyuan
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container_issue 2
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container_title Cell biochemistry and biophysics
container_volume 65
creator Zhao, Shu
Yang, Huike
Zhang, Minghui
Zhang, Dekai
Liu, Yupeng
Liu, Yan
Song, Ying
Zhang, Xiaosan
Li, Hongbin
Ma, Wenjie
Zhang, Qingyuan
description In order to investigate the prognostic value of circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC), the blood cells from 98 MBC patients and 60 controls were evaluated by RT-PCR to detect the presence of markers EpCAM , CK19 , and hMAM . Peripheral blood was obtained from all patients with MBC before any systemic therapy. Immunofluorescence staining experiment was conducted on CTCs samples from 10 patients to investigate the coexpression of EpCAM, CK19, and hMAM. In addition, analyses were carried out for their correlation with patients’ clinicopathologic features. EpCAM +, CK19 +, and hMAM + cells were detected in 50 (51.0 %), 43 (43.9 %), and 68 (69.4 %) of the 98 patients, respectively. Triple-marker-positive CTCs were detected in 86 of 98 (87.8 %) patients with a significantly higher rate than the control group. Among the 98 patients, 12 (12.2 %) patients were negative for three genes, 34 (34.7 %) positive for one gene, 29 (29.6 %) positive for any two genes, and 23 (23.5 %) positive for all three genes. Compared to single-marker detection, the triple combined marker detection exhibited significantly higher rate. Furthermore, the specificity of triple combined markers of serial test was 100 %. The expression of three genes was significantly correlated with lymph node metastasis, high histological grade, and high levels of serum CA153 and CEA. Double-immunofluorescence labeling confirmed the presence of following CTCs phenotypes: CK19+/hMAM+, CK19+/hMAM−, CK19−/hMAM+, CK19+/EpCAM+, CK19−/EpCAM+, CK19+/EpCAM−, hMAM+/EpCAM+, and hMAM+/EpCAM−. After 2 years of follow-up, the presence of CTCs with triple-marker positive in peripheral blood was an independent risk factor for reduced progression-free survival (PFS) and overall survival (OS), and the presence of CTCs before any chemotherapy predicts poor OS and PFS in patients with MBC.
doi_str_mv 10.1007/s12013-012-9426-2
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Peripheral blood was obtained from all patients with MBC before any systemic therapy. Immunofluorescence staining experiment was conducted on CTCs samples from 10 patients to investigate the coexpression of EpCAM, CK19, and hMAM. In addition, analyses were carried out for their correlation with patients’ clinicopathologic features. EpCAM +, CK19 +, and hMAM + cells were detected in 50 (51.0 %), 43 (43.9 %), and 68 (69.4 %) of the 98 patients, respectively. Triple-marker-positive CTCs were detected in 86 of 98 (87.8 %) patients with a significantly higher rate than the control group. Among the 98 patients, 12 (12.2 %) patients were negative for three genes, 34 (34.7 %) positive for one gene, 29 (29.6 %) positive for any two genes, and 23 (23.5 %) positive for all three genes. Compared to single-marker detection, the triple combined marker detection exhibited significantly higher rate. Furthermore, the specificity of triple combined markers of serial test was 100 %. The expression of three genes was significantly correlated with lymph node metastasis, high histological grade, and high levels of serum CA153 and CEA. Double-immunofluorescence labeling confirmed the presence of following CTCs phenotypes: CK19+/hMAM+, CK19+/hMAM−, CK19−/hMAM+, CK19+/EpCAM+, CK19−/EpCAM+, CK19+/EpCAM−, hMAM+/EpCAM+, and hMAM+/EpCAM−. After 2 years of follow-up, the presence of CTCs with triple-marker positive in peripheral blood was an independent risk factor for reduced progression-free survival (PFS) and overall survival (OS), and the presence of CTCs before any chemotherapy predicts poor OS and PFS in patients with MBC.</description><identifier>ISSN: 1085-9195</identifier><identifier>EISSN: 1559-0283</identifier><identifier>DOI: 10.1007/s12013-012-9426-2</identifier><identifier>PMID: 22990361</identifier><language>eng</language><publisher>New York: Springer-Verlag</publisher><subject>Adult ; Aged ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - metabolism ; Biochemistry ; Biological and Medical Physics ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biophysics ; Biotechnology ; Breast Neoplasms - blood ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Cell Adhesion Molecules - genetics ; Cell Adhesion Molecules - metabolism ; Cell Biology ; Clinical outcomes ; Disease-Free Survival ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Epithelial Cell Adhesion Molecule ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Keratin-19 - genetics ; Keratin-19 - metabolism ; Life Sciences ; Lymphatic Metastasis ; Microscopy, Fluorescence ; Middle Aged ; Neoplastic Cells, Circulating - metabolism ; Pharmacology/Toxicology ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Sensitivity and Specificity ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Translational Biomedical Research</subject><ispartof>Cell biochemistry and biophysics, 2013-03, Vol.65 (2), p.263-273</ispartof><rights>Springer Science+Business Media New York 2012</rights><rights>Springer Science+Business Media New York 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-26ba1ffc2d3f7b93b92b8989fea66287c1b44462216e2a903aea69d81675c67b3</citedby><cites>FETCH-LOGICAL-c372t-26ba1ffc2d3f7b93b92b8989fea66287c1b44462216e2a903aea69d81675c67b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12013-012-9426-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12013-012-9426-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22990361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Shu</creatorcontrib><creatorcontrib>Yang, Huike</creatorcontrib><creatorcontrib>Zhang, Minghui</creatorcontrib><creatorcontrib>Zhang, Dekai</creatorcontrib><creatorcontrib>Liu, Yupeng</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Song, Ying</creatorcontrib><creatorcontrib>Zhang, Xiaosan</creatorcontrib><creatorcontrib>Li, Hongbin</creatorcontrib><creatorcontrib>Ma, Wenjie</creatorcontrib><creatorcontrib>Zhang, Qingyuan</creatorcontrib><title>Circulating Tumor Cells (CTCs) Detected by Triple-Marker EpCAM, CK19, and hMAM RT-PCR and Their Relation to Clinical Outcome in Metastatic Breast Cancer Patients</title><title>Cell biochemistry and biophysics</title><addtitle>Cell Biochem Biophys</addtitle><addtitle>Cell Biochem Biophys</addtitle><description>In order to investigate the prognostic value of circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC), the blood cells from 98 MBC patients and 60 controls were evaluated by RT-PCR to detect the presence of markers EpCAM , CK19 , and hMAM . 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Peripheral blood was obtained from all patients with MBC before any systemic therapy. Immunofluorescence staining experiment was conducted on CTCs samples from 10 patients to investigate the coexpression of EpCAM, CK19, and hMAM. In addition, analyses were carried out for their correlation with patients’ clinicopathologic features. EpCAM +, CK19 +, and hMAM + cells were detected in 50 (51.0 %), 43 (43.9 %), and 68 (69.4 %) of the 98 patients, respectively. Triple-marker-positive CTCs were detected in 86 of 98 (87.8 %) patients with a significantly higher rate than the control group. Among the 98 patients, 12 (12.2 %) patients were negative for three genes, 34 (34.7 %) positive for one gene, 29 (29.6 %) positive for any two genes, and 23 (23.5 %) positive for all three genes. Compared to single-marker detection, the triple combined marker detection exhibited significantly higher rate. Furthermore, the specificity of triple combined markers of serial test was 100 %. The expression of three genes was significantly correlated with lymph node metastasis, high histological grade, and high levels of serum CA153 and CEA. Double-immunofluorescence labeling confirmed the presence of following CTCs phenotypes: CK19+/hMAM+, CK19+/hMAM−, CK19−/hMAM+, CK19+/EpCAM+, CK19−/EpCAM+, CK19+/EpCAM−, hMAM+/EpCAM+, and hMAM+/EpCAM−. After 2 years of follow-up, the presence of CTCs with triple-marker positive in peripheral blood was an independent risk factor for reduced progression-free survival (PFS) and overall survival (OS), and the presence of CTCs before any chemotherapy predicts poor OS and PFS in patients with MBC.</abstract><cop>New York</cop><pub>Springer-Verlag</pub><pmid>22990361</pmid><doi>10.1007/s12013-012-9426-2</doi><tpages>11</tpages></addata></record>
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subjects Adult
Aged
Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
Biochemistry
Biological and Medical Physics
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biophysics
Biotechnology
Breast Neoplasms - blood
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Biology
Clinical outcomes
Disease-Free Survival
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epithelial Cell Adhesion Molecule
Female
Gene Expression Regulation, Neoplastic
Humans
Keratin-19 - genetics
Keratin-19 - metabolism
Life Sciences
Lymphatic Metastasis
Microscopy, Fluorescence
Middle Aged
Neoplastic Cells, Circulating - metabolism
Pharmacology/Toxicology
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Sensitivity and Specificity
Transcription Factors - genetics
Transcription Factors - metabolism
Translational Biomedical Research
title Circulating Tumor Cells (CTCs) Detected by Triple-Marker EpCAM, CK19, and hMAM RT-PCR and Their Relation to Clinical Outcome in Metastatic Breast Cancer Patients
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