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Collective invasion in ductal and lobular breast cancer associates with distant metastasis

Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary i...

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Autores principales: Khalil, Antoine A., Ilina, Olga, Gritsenko, Pavlo G., Bult, Peter, Span, Paul N., Friedl, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711975/
https://www.ncbi.nlm.nih.gov/pubmed/28894989
http://dx.doi.org/10.1007/s10585-017-9858-6
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author Khalil, Antoine A.
Ilina, Olga
Gritsenko, Pavlo G.
Bult, Peter
Span, Paul N.
Friedl, Peter
author_facet Khalil, Antoine A.
Ilina, Olga
Gritsenko, Pavlo G.
Bult, Peter
Span, Paul N.
Friedl, Peter
author_sort Khalil, Antoine A.
collection PubMed
description Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary invasive ductal carcinoma (IDC), expressing E-cadherin, and E-cadherin negative invasive lobular carcinoma (ILC) and identified predominantly collective invasion patterns (86/86 samples) in both carcinoma types. Whereas collective invasion in IDC lesions retained adherens junctions, multicellular clusters and “Indian files” in ILC, despite the absence of adherens junctions (AJ) proteins E-cadherin and β-catenin, retained CD44 at cell–cell contacts. By histomorphological scoring and semi-automated image analysis, we show that the extent of collective invasion into the adipose tissue correlated with decreased distant metastasis-free survival (5-year follow-up; hazard ratio: 2.32 and 2.29, respectively). Thus, collective invasion represents the predominant invasion mode in breast cancer, develops distinct junctional subtypes in IDC and ILC, and associates with distant metastasis, suggesting a critical role in systemic dissemination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10585-017-9858-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-57119752017-12-07 Collective invasion in ductal and lobular breast cancer associates with distant metastasis Khalil, Antoine A. Ilina, Olga Gritsenko, Pavlo G. Bult, Peter Span, Paul N. Friedl, Peter Clin Exp Metastasis Research Paper Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary invasive ductal carcinoma (IDC), expressing E-cadherin, and E-cadherin negative invasive lobular carcinoma (ILC) and identified predominantly collective invasion patterns (86/86 samples) in both carcinoma types. Whereas collective invasion in IDC lesions retained adherens junctions, multicellular clusters and “Indian files” in ILC, despite the absence of adherens junctions (AJ) proteins E-cadherin and β-catenin, retained CD44 at cell–cell contacts. By histomorphological scoring and semi-automated image analysis, we show that the extent of collective invasion into the adipose tissue correlated with decreased distant metastasis-free survival (5-year follow-up; hazard ratio: 2.32 and 2.29, respectively). Thus, collective invasion represents the predominant invasion mode in breast cancer, develops distinct junctional subtypes in IDC and ILC, and associates with distant metastasis, suggesting a critical role in systemic dissemination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10585-017-9858-6) contains supplementary material, which is available to authorized users. Springer Netherlands 2017-09-11 2017 /pmc/articles/PMC5711975/ /pubmed/28894989 http://dx.doi.org/10.1007/s10585-017-9858-6 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research Paper
Khalil, Antoine A.
Ilina, Olga
Gritsenko, Pavlo G.
Bult, Peter
Span, Paul N.
Friedl, Peter
Collective invasion in ductal and lobular breast cancer associates with distant metastasis
title Collective invasion in ductal and lobular breast cancer associates with distant metastasis
title_full Collective invasion in ductal and lobular breast cancer associates with distant metastasis
title_fullStr Collective invasion in ductal and lobular breast cancer associates with distant metastasis
title_full_unstemmed Collective invasion in ductal and lobular breast cancer associates with distant metastasis
title_short Collective invasion in ductal and lobular breast cancer associates with distant metastasis
title_sort collective invasion in ductal and lobular breast cancer associates with distant metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711975/
https://www.ncbi.nlm.nih.gov/pubmed/28894989
http://dx.doi.org/10.1007/s10585-017-9858-6
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