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Breast Cancer Res Treat. 2019 Apr;174(2):387-399. doi: 10.1007/s10549-018-05085-9. Epub 2018 Dec 15.

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

Author information

1
Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
2
Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
3
Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-kom, Al Minufiyah, Egypt.
4
Department of Histopathology, School of Medicine, Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK.
5
Cancer Biology and Translational Research, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK.
6
Department of Pharmacology, Weill Cornell Medicine, 10065, New York, NY, USA.
7
Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK. Emad.Rakha@nottingham.ac.uk.
8
Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-kom, Al Minufiyah, Egypt. Emad.Rakha@nottingham.ac.uk.
9
Department of Histopathology, School of Medicine, Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK. Emad.Rakha@nottingham.ac.uk.

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.

KEYWORDS:

CD133; Cancer Stem Cell; Invasive breast cancer; Prognosis

PMID:
30554343
DOI:
10.1007/s10549-018-05085-9
[Indexed for MEDLINE]

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