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Cancers 2013, 5(4), 1485-1503; doi:10.3390/cancers5041485
Article

Heterogeneity of Mesenchymal Markers Expression—Molecular Profiles of Cancer Cells Disseminated by Lymphatic and Hematogenous Routes in Breast Cancer

1,2
, 1
, 3
, 3,4
, 5
, 6
 and 1,*
1 Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-211, Poland 2 Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw 02-091, Poland 3 Bank of Frozen Tissues and Genetic Specimens, Department of Medical Laboratory Diagnostics, Medical University of Gdańsk, Gdańsk 80-211, Poland 4 Department of Surgical Oncology, Medical University of Gdańsk, Gdańsk 80-214, Poland 5 Department of Pathomorphology, Medical University of Gdańsk, Gdańsk 80-214, Poland 6 Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk 80-211, Poland
* Author to whom correspondence should be addressed.
Received: 29 August 2013 / Revised: 7 October 2013 / Accepted: 1 November 2013 / Published: 8 November 2013
(This article belongs to the Special Issue Circulating Tumor Cells in Cancers)
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Abstract

Breast cancers can metastasize via hematogenous and lymphatic routes, however in some patients only one type of metastases are detected, suggesting a certain proclivity in metastatic patterns. Since epithelial-mesenchymal transition (EMT) plays an important role in cancer dissemination it would be worthwhile to find if a specific profile of EMT gene expression exists that is related to either lymphatic or hematogenous dissemination. Our study aimed at evaluating gene expression profile of EMT-related markers in primary tumors (PT) and correlated them with the pattern of metastatic spread. From 99 early breast cancer patients peripheral blood samples (N = 99), matched PT (N = 47) and lymph node metastases (LNM; N = 22) were collected. Expression of TWIST1, SNAI1, SNAI2 and VIM was analyzed in those samples. Additionally expression of CK19, MGB1 and HER2 was measured in CTCs-enriched blood fractions (CTCs-EBF). Results were correlated with each other and with clinico-pathological data of the patients. Results show that the mesenchymal phenotype of CTCs-EBF correlated with poor clinico-pathological characteristics of the patients. Additionally, PT shared more similarities with LNM than with CTCs-EBF. Nevertheless, LNM showed increased expression of EMT-related markers than PT; and EMT itself in PT did not seem to be necessary for lymphatic dissemination.
Keywords: breast cancer; lymph node metastasis; circulating tumor cells; metastasis; cancer dissemination; epithelial-mesenchymal transition breast cancer; lymph node metastasis; circulating tumor cells; metastasis; cancer dissemination; epithelial-mesenchymal transition
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Markiewicz, A.; Książkiewicz, M.; Seroczyńska, B.; Skokowski, J.; Szade, J.; Wełnicka-Jaśkiewicz, M.; Zaczek, A.J. Heterogeneity of Mesenchymal Markers Expression—Molecular Profiles of Cancer Cells Disseminated by Lymphatic and Hematogenous Routes in Breast Cancer. Cancers 2013, 5, 1485-1503.

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