Research article

The CD44⁺/CD24^- phenotype is enriched in basal-like breast tumors

Gabriella Honeth¹ , Pär-Ola Bendahl¹ , Markus Ringnér^1,2 , Lao H Saal^1,3 , Sofia K Gruvberger-Saal^1,3 , Kristina Lövgren¹ , Dorthe Grabau⁴ , Mårten Fernö¹ , Åke Borg^1,2,5 and Cecilia Hegardt^1,2,5

¹  Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden

²  CREATE Health Strategic Centre for Clinical Cancer Research, Klinikgatan 28, SE-221 85 Lund, Sweden

³  Institute for Cancer Genetics, Columbia University, 1150 St Nicholas Ave, New York, NY 10032, USA

⁴  Department of Pathology, Clinical Sciences, Lund University, Sölvegatan 25, SE-221 85 Lund, Sweden

⁵  Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Klinikgatan 26, SE-221 85 Lund, Sweden

author email corresponding author email

Breast Cancer Research 2008, 10:R53doi:10.1186/bcr2108

Published:	17 June 2008

See related editorial by Dontu, http://breast-cancer-research.com/content/10/5/110

Abstract

Introduction

Human breast tumors are heterogeneous and consist of phenotypically diverse cells. Breast cancer cells with a CD44⁺/CD24^- phenotype have been suggested to have tumor-initiating properties with stem cell-like and invasive features, although it is unclear whether their presence within a tumor has clinical implications. There is also a large heterogeneity between tumors, illustrated by reproducible stratification into various subtypes based on gene expression profiles or histopathological features. We have explored the prevalence of cells with different CD44/CD24 phenotypes within breast cancer subtypes.

Methods

Double-staining immunohistochemistry was used to quantify CD44 and CD24 expression in 240 human breast tumors for which information on other tumor markers and clinical characteristics was available. Gene expression data were also accessible for a cohort of the material.

Results

A considerable heterogeneity in CD44 and CD24 expression was seen both between and within tumors. A complete lack of both proteins was evident in 35% of the tumors, while 13% contained cells of more than one of the CD44⁺/CD24^-, CD44^-/CD24⁺ and CD44⁺/CD24⁺ phenotypes. CD44⁺/CD24^- cells were detected in 31% of the tumors, ranging in proportion from only a few to close to 100% of tumor cells. The CD44⁺/CD24^- phenotype was most common in the basal-like subgroup – characterized as negative for the estrogen and progesterone receptors as well as for HER2, and as positive for cytokeratin 5/14 and/or epidermal growth factor receptor, and particularly common in BRCA1 hereditary tumors, of which 94% contained CD44⁺/CD24^- cells. The CD44⁺/CD24^- phenotype was surprisingly scarce in HER2+ tumors, which had a predominantly CD24⁺ status. A CD44⁺/CD24^- gene expression signature was generated, which included CD44 and α₆-integrin (CD49f) among the top-ranked overexpressed genes.

Conclusion

We demonstrate an association between basal-like and particularly BRCA1 hereditary breast cancer and the presence of CD44⁺/CD24^- cells. Not all basal-like tumors and very few HER2+ tumors, however, contain CD44⁺/CD24^- cells, emphasizing that a putative tumorigenic ability may not be confined to cells of this phenotype and that other breast cancer stem cell markers remain to be identified.