Abstract
CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC. CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated. High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038). This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.
Highlights
Breast Cancer (BC) is a heterogeneous disease with significant clinical, pathological and molecular diversities between tumours
CD133 genomic profiling High CD133 mRNA expression was associated with high histological grade (p
High CD133 mRNA expression was associated with negative ER and progesterone receptor (PgR) status, younger age at diagnosis and premenopausal women (p
Summary
Breast Cancer (BC) is a heterogeneous disease with significant clinical, pathological and molecular diversities between tumours. Breast CSCs are proposed to have a key role in primary tumourigenesis and may contribute to tumour heterogeneity [2,3]. In vitro studies using BRCA1-associated BC cell lines contain CD44+/CD24low and CD133+ cells, displayed CSC properties such as elevated rate of proliferation and tumour forming capability [4]. Evaluation of such CSC markers in BC at the protein levels such as ALDH1 and CD44+/CD24low expression showed association with high histological grade, high proliferative activity and oestrogen receptor (ER) negativity [5]. Microarray gene expression data mining using CD44+/CD24low/- tumour cells against normal breast epithelium resulted in the development of CSC signatures, enabling prediction of distant metastasis free survival in independent patient datasets [6,7]
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