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dc.contributor.authorAli, Razaen
dc.contributor.authorDawson, Sarah-Janeen
dc.contributor.authorBlows, Fiona Men
dc.contributor.authorProvenzano, Elenaen
dc.contributor.authorPharoah, Paulen
dc.contributor.authorCaldas, Carlosen
dc.date.accessioned2011-12-23T06:04:55Z
dc.date.available2011-12-23T06:04:55Z
dc.date.issued2011-11-23en
dc.identifier.issn1465-542X
dc.identifier.urihttp://www.dspace.cam.ac.uk/handle/1810/240965
dc.description.abstractINTRODUCTION: 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.
dc.languageengen
dc.publisherBMC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAgeden
dc.subjectBiomarkers, Tumoren
dc.subjectBreasten
dc.subjectBreast Neoplasmsen
dc.subjectCluster Analysisen
dc.subjectCohort Studiesen
dc.subjectFemaleen
dc.subjectGene Expression Profilingen
dc.subjectHumansen
dc.subjectImmunophenotypingen
dc.subjectMiddle Ageden
dc.subjectNeoplasm Stagingen
dc.subjectNeoplastic Stem Cellsen
dc.subjectPrognosisen
dc.subjectReceptors, Estrogenen
dc.subjectSurvival Analysisen
dc.subjectYoung Adulten
dc.titleCancer stem cell markers in breast cancer: pathological, clinical and prognostic significanceen
dc.typeArticle
dc.date.updated2011-12-23T06:04:56Z
dc.language.rfc3066en
dc.rights.holderAli et al.; licensee BioMed Central Ltd.
prism.endingPageR118
prism.issueIdentifier6en
prism.publicationDate2011en
prism.publicationNameBreast Cancer Researchen
prism.startingPageR118
prism.volume13en
dcterms.dateAccepted2011-11-23en
rioxxterms.versionofrecord10.1186/bcr3061en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2011-11-23en
dc.contributor.orcidAli, Raza [0000-0001-7587-0906]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidCaldas, Carlos [0000-0003-3547-1489]
dc.identifier.eissn1465-542X
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2011-11-23en


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International