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Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells
INTRODUCTION: The presence of circulating tumor cells (CTC) in breast cancer might be associated with stem cell-like tumor cells which have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, to be able to disseminate and metastasize, CTC must be able to perfo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496132/ https://www.ncbi.nlm.nih.gov/pubmed/22264265 http://dx.doi.org/10.1186/bcr3099 |
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author | Kasimir-Bauer, Sabine Hoffmann, Oliver Wallwiener, Diethelm Kimmig, Rainer Fehm, Tanja |
author_facet | Kasimir-Bauer, Sabine Hoffmann, Oliver Wallwiener, Diethelm Kimmig, Rainer Fehm, Tanja |
author_sort | Kasimir-Bauer, Sabine |
collection | PubMed |
description | INTRODUCTION: The presence of circulating tumor cells (CTC) in breast cancer might be associated with stem cell-like tumor cells which have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, to be able to disseminate and metastasize, CTC must be able to perform epithelial-mesenchymal transition (EMT). We studied the expression of three EMT markers and the stem cell marker ALDH1 in CTC from 502 primary breast cancer patients. Data were correlated with the presence of disseminated tumor cells (DTC) in the bone marrow (BM) and with clinicopathological data of the patients. METHODS: A total of 2 × 5 ml of blood was analyzed for CTC with the AdnaTest BreastCancer (AdnaGen AG) for the detection of EpCAM, MUC-1, HER2 and beta-Actin transcripts. The recovered c-DNA was additionally multiplex tested for three EMT markers [TWIST1, Akt2, phosphoinositide kinase-3 (PI3Kα)] and separately for the tumor stem cell marker ALDH1. The identification of EMT markers was considered positive if at least one marker was detected in the sample. Two BM aspirates from all patients were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. RESULTS: Ninety-seven percent of 30 healthy donor samples investigated were negative for EMT and 95% for ALDH1 transcripts, respectively. CTC were detected in 97/502 (19%) patients. At least one of the EMT markers was expressed in 29% and ALDH1 was present in 14% of the samples, respectively. Interestingly, 5% of the ALDH1-positive and 18% of the EMT-positive patients were CTC-negative based on the cut-off level determined for CTC-positivity applying the AdnaTest BreastCancer. DTC in the BM were detected in 107/502 (21%) patients and no correlation was found between BM status and CTC positivity (P = 0.41). The presence of CTC, EMT and ALDH1 expression was not correlated to any of the prognostic clinical markers. CONCLUSIONS: Our data indicate that (1) a subset of primary breast cancer patients shows EMT and stem cell characteristics and (2) the currently used detection methods for CTC are not efficient to identify a subtype of CTC which underwent EMT. (3) The clinical relevance on prognosis and therapy response has to be further evaluated in a prospective trial. |
format | Online Article Text |
id | pubmed-3496132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34961322012-11-14 Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells Kasimir-Bauer, Sabine Hoffmann, Oliver Wallwiener, Diethelm Kimmig, Rainer Fehm, Tanja Breast Cancer Res Research Article INTRODUCTION: The presence of circulating tumor cells (CTC) in breast cancer might be associated with stem cell-like tumor cells which have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, to be able to disseminate and metastasize, CTC must be able to perform epithelial-mesenchymal transition (EMT). We studied the expression of three EMT markers and the stem cell marker ALDH1 in CTC from 502 primary breast cancer patients. Data were correlated with the presence of disseminated tumor cells (DTC) in the bone marrow (BM) and with clinicopathological data of the patients. METHODS: A total of 2 × 5 ml of blood was analyzed for CTC with the AdnaTest BreastCancer (AdnaGen AG) for the detection of EpCAM, MUC-1, HER2 and beta-Actin transcripts. The recovered c-DNA was additionally multiplex tested for three EMT markers [TWIST1, Akt2, phosphoinositide kinase-3 (PI3Kα)] and separately for the tumor stem cell marker ALDH1. The identification of EMT markers was considered positive if at least one marker was detected in the sample. Two BM aspirates from all patients were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. RESULTS: Ninety-seven percent of 30 healthy donor samples investigated were negative for EMT and 95% for ALDH1 transcripts, respectively. CTC were detected in 97/502 (19%) patients. At least one of the EMT markers was expressed in 29% and ALDH1 was present in 14% of the samples, respectively. Interestingly, 5% of the ALDH1-positive and 18% of the EMT-positive patients were CTC-negative based on the cut-off level determined for CTC-positivity applying the AdnaTest BreastCancer. DTC in the BM were detected in 107/502 (21%) patients and no correlation was found between BM status and CTC positivity (P = 0.41). The presence of CTC, EMT and ALDH1 expression was not correlated to any of the prognostic clinical markers. CONCLUSIONS: Our data indicate that (1) a subset of primary breast cancer patients shows EMT and stem cell characteristics and (2) the currently used detection methods for CTC are not efficient to identify a subtype of CTC which underwent EMT. (3) The clinical relevance on prognosis and therapy response has to be further evaluated in a prospective trial. BioMed Central 2012 2012-01-20 /pmc/articles/PMC3496132/ /pubmed/22264265 http://dx.doi.org/10.1186/bcr3099 Text en Copyright ©2012 Kasimir-Bauer et a.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kasimir-Bauer, Sabine Hoffmann, Oliver Wallwiener, Diethelm Kimmig, Rainer Fehm, Tanja Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells |
title | Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells |
title_full | Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells |
title_fullStr | Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells |
title_full_unstemmed | Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells |
title_short | Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells |
title_sort | expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496132/ https://www.ncbi.nlm.nih.gov/pubmed/22264265 http://dx.doi.org/10.1186/bcr3099 |
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