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

Honeth, Gabriella LU ; Bendahl, Pär-Ola LU ; Ringnér, Markus LU ; Saal, Lao LU ; Gruvberger, Sofia LU ; Lövgren, Kristina LU ; Grabau, Dorthe LU ; Fernö, Mårten LU ; Borg, Åke LU and Hegardt, Cecilia LU (2008) In Breast Cancer Research 10(3).
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... (More)
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 alpha(6)-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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research
volume
10
issue
3
publisher
BioMed Central
external identifiers
  • wos:000257869600021
  • scopus:55749104730
ISSN
1465-5411
DOI
10.1186/bcr2108
project
CREATE Health
language
English
LU publication?
yes
id
aea8e5bf-d945-48cc-97a8-49c256e29693 (old id 1253937)
date added to LUP
2008-11-04 09:56:38
date last changed
2017-11-12 03:24:49
@article{aea8e5bf-d945-48cc-97a8-49c256e29693,
  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 alpha(6)-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.},
  articleno    = {R53},
  author       = {Honeth, Gabriella and Bendahl, Pär-Ola and Ringnér, Markus and Saal, Lao and Gruvberger, Sofia and Lövgren, Kristina and Grabau, Dorthe and Fernö, Mårten and Borg, Åke and Hegardt, Cecilia},
  issn         = {1465-5411},
  language     = {eng},
  number       = {3},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {The CD44(+)/CD24(-) phenotype is enriched in basal-like breast tumors},
  url          = {http://dx.doi.org/10.1186/bcr2108},
  volume       = {10},
  year         = {2008},
}