Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer.

Abstract

PURPOSE:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: Chitra Joseph, Maariya Arshad, Sasagu Kurozomi, Maryam Althobiti, Islam M Miligy, Sara Al-Izzi, Michael S Toss, Fang Qin Goh, Simon J Johnston, Stewart G Martin, Ian O Ellis, Nigel P Mongan, Andrew R Green, Emad A Rakha
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 174 Issue 2 Pg. 387-399 (Apr 2019) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 30554343 (Publication Type: Journal Article)

Chemical References

• AC133 Antigen
• Biomarkers, Tumor
• PROM1 protein, human
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• AC133 Antigen (genetics, metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Proliferation
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Multivariate Analysis
• Neoplasm Grading
• Neoplastic Stem Cells (metabolism, pathology)
• Prognosis
• Proteomics
• Receptor, ErbB-2 (genetics)
• Tumor Burden
• Up-Regulation