Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
IntroductionThe 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 complied with REMARK criteria.
Results:
In ER- 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 0-2 years follow up, 2.4; 95% confidence interval (95% CI), 1.2 - 4.8; p=0.009). The composite 'Total CSC'score carried independent prognostic significance in ER- cases for the first 4 years of follow-up (HR for 0-4 years follow-up, 1.3; 95% CI, 1.1 - 1.6; p=0.006).
Conclusion:
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- disease. The use of multiple markers to identify tumours enriched for CSCs has 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.
Author: Hamid AliSarah-Jane DawsonFiona BlowsElena ProvenzanoPaul PharoahCarlos Caldas
Credits/Source: Breast Cancer Research 2011, 13:R118
Published on: 2011-11-23
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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