Breast Cancer Research and Treatment

, Volume 133, Issue 3, pp 979–995 | Cite as

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

  • Mohamed A. H. Ahmed
  • Mohammed A. Aleskandarany
  • Emad A. Rakha
  • Radwa Z. A. Moustafa
  • Ahmed Benhasouna
  • Christopher Nolan
  • Andrew R. Green
  • Mohammad Ilyas
  • Ian O. Ellis
Preclinical study

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.

Keywords

CD24 CD44 Immunohistochemistry Stem Cells Breast Cancer Prognosis 

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

Notes

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.

Supplementary material

10549_2011_1865_MOESM1_ESM.tif (753 kb)
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)
10549_2011_1865_MOESM2_ESM.doc (76 kb)
Supplementary material 2 (DOC 76 kb)
10549_2011_1865_MOESM3_ESM.doc (96 kb)
Supplementary material 3 (DOC 96 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Mohamed A. H. Ahmed
    • 1
    • 2
  • Mohammed A. Aleskandarany
    • 1
    • 3
  • Emad A. Rakha
    • 1
    • 4
  • Radwa Z. A. Moustafa
    • 5
  • Ahmed Benhasouna
    • 1
  • Christopher Nolan
    • 1
  • Andrew R. Green
    • 1
  • Mohammad Ilyas
    • 1
    • 4
  • Ian O. Ellis
    • 1
    • 4
  1. 1.Division of Pathology, School of Molecular Medical SciencesUniversity of NottinghamNottinghamUK
  2. 2.Department of Pathology, Faculty of MedicineSuez Canal UniversityIsmailiaEgypt
  3. 3.Pathology DepartmentMenoufyia UniversityShibin el KomEgypt
  4. 4.Department of HistopathologyNottingham City Hospital NHS TrustNottinghamUK
  5. 5.Egyptian Ministry of HealthIsmailiaEgypt

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