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A CD44−/CD24+ phenotype is a poor prognostic marker in early invasive breast cancer

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Abstract

A CD44−/CD24+ phenotype is a poor prognostic marker in early invasive breast cancer. Breast cancer cells with high CD44 and low or absent CD24 (i.e. CD44+CD24−/low phenotype) are reported to have stem cell features. However, the clinical impact of CD24 and CD44 expression in tumours remains unclear. To explore the immunohistochemical expression of CD44 and CD24 (individually and combined) and their clinical value as prognostic and predictive markers. Immunohistochemical expression of CD24 and CD44 was studied in a large series of early primary invasive breast cancer tumours (n = 1036) prepared as a tissue microarray. Associations between the expression of each marker individually and in combination and clinico-pathological, molecular variables and patients’ outcome were investigated. CD24 cytoplasmic expression was significantly associated with poor prognostic variables including high tumour grade, ER−, PR−, HER2+, p53+ and triple negative (TN) phenotype; P < 0.05. However, CD24 expression was not significantly associated with patients’ outcome. Conversely, CD44 expression was associated with favourable prognostic criteria including lower Nottingham prognostic index, ER+, HER2− and luminal phenotype; P < 0.05. Moreover, CD44 expression was found to be an independent predictor of good prognosis. In combination, the CD44+/CD24− phenotype was associated with the most favourable outcome (84 and 80% 10 year breast cancer survival [BCSS] and metastasis free survival [MFS], respectively). Contrasting this, the CD44−/CD24+ phenotype was associated with the most dismal outcome (62 and 60% 10 years BCSS and MFS, respectively). CD24 and CD44 expression can individually yield prognostic data in breast cancer, but importantly, when both markers are considered; the CD44+/CD24− phenotype had the best prognosis, while the CD44−/CD24+ phenotype had the worst prognosis. This shows that the relationship between basic cell biology and clinical behaviour is not always straightforward and warrants further investigations of the true clinical impact of breast cancer stem cells.

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Abbreviations

AR:

Androgen receptor

BC:

Breast cancer

BCSS:

Breast cancer-specific survival

BLBC:

Basal-like breast cancer

CK:

Cytokeratin

CSC:

Cancer stem cells

DAB:

3,3′-Diaminobenzidine

EGFR:

Epidermal growth factor receptor

ECL:

Enhanced chemiluminescence

ER:

Oestrogen receptor

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

IHC:

Immunohistochemistry

KD:

Kilodalton

LR:

Log rank

MFS:

Metastasis free survival

NPI:

Nottingham prognostic index

PBS:

Phosphate buffered saline

PR:

Progesterone receptor

REMARK:

Reporting recommendations for tumour marker prognostic studies

TBS:

Tris-buffered saline

TMA:

Tissue microarray

TN:

Triple negative

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Acknowledgments

We thank Professor Peter Altvoget for the generous gift of anti-CD24 (SWA11) antibody. We also thank the Ministry of Higher Education (Egypt) for funding Mohamed Ahmed and M. Aleskandarany.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, UK

    Mohamed A. H. Ahmed, Mohammed A. Aleskandarany, Emad A. Rakha, Ahmed Benhasouna, Christopher Nolan, Andrew R. Green, Mohammad Ilyas & Ian O. Ellis

  2. Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Mohamed A. H. Ahmed

  3. Pathology Department, Menoufyia University, Shibin el Kom, Egypt

    Mohammed A. Aleskandarany

  4. Department of Histopathology, Nottingham City Hospital NHS Trust, Hucknall Road, Nottingham, NG5 1PB, UK

    Emad A. Rakha, Mohammad Ilyas & Ian O. Ellis

  5. Egyptian Ministry of Health, Ismailia, Egypt

    Radwa Z. A. Moustafa

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  1. Mohamed A. H. Ahmed
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  2. Mohammed A. Aleskandarany
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Corresponding author

Correspondence to Ian O. Ellis.

Electronic supplementary material

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10549_2011_1865_MOESM1_ESM.tif

Supplementary Fig. 1: CD24 Nuclear expression. TMA core showing nuclear immunohistochemical expression of CD24; (A): X100, and (B): ×200. (C) and (D): Kaplan–Meier survival plot for patients’ BCSS and MFS for nuclear expression of CD24. Supplementary material 1 (EPS 2849 kb)

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Supplementary material 3 (DOC 96 kb)

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Ahmed, M.A.H., Aleskandarany, M.A., Rakha, E.A. et al. A CD44−/CD24+ phenotype is a poor prognostic marker in early invasive breast cancer. Breast Cancer Res Treat 133, 979–995 (2012). https://doi.org/10.1007/s10549-011-1865-8

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  • DOI: https://doi.org/10.1007/s10549-011-1865-8

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