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Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance

INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by...

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Autores principales: Ali, H Raza, Dawson, Sarah-Jane, Blows, Fiona M, Provenzano, Elena, Pharoah, Paul D, Caldas, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326560/
https://www.ncbi.nlm.nih.gov/pubmed/22112299
http://dx.doi.org/10.1186/bcr3061
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author Ali, H Raza
Dawson, Sarah-Jane
Blows, Fiona M
Provenzano, Elena
Pharoah, Paul D
Caldas, Carlos
author_facet Ali, H Raza
Dawson, Sarah-Jane
Blows, Fiona M
Provenzano, Elena
Pharoah, Paul D
Caldas, Carlos
author_sort Ali, H Raza
collection PubMed
description INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC). METHODS: We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria. RESULTS: In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006). CONCLUSIONS: Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs.
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spelling pubmed-33265602012-04-16 Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance Ali, H Raza Dawson, Sarah-Jane Blows, Fiona M Provenzano, Elena Pharoah, Paul D Caldas, Carlos Breast Cancer Res Research Article INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC). METHODS: We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria. RESULTS: In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006). CONCLUSIONS: Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs. BioMed Central 2011 2011-11-23 /pmc/articles/PMC3326560/ /pubmed/22112299 http://dx.doi.org/10.1186/bcr3061 Text en Copyright ©2011 Ali et al.; 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
Ali, H Raza
Dawson, Sarah-Jane
Blows, Fiona M
Provenzano, Elena
Pharoah, Paul D
Caldas, Carlos
Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
title Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
title_full Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
title_fullStr Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
title_full_unstemmed Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
title_short Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
title_sort cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326560/
https://www.ncbi.nlm.nih.gov/pubmed/22112299
http://dx.doi.org/10.1186/bcr3061
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