title: CD44(+)/CD24(-/low) cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome.
abstract: Women classified as having triple-negative tumors have a poor prognosis. The importance of CD44(+)/CD24(-/low) (stem/progenitor cell-phenotype) in breast cancer patients has also been appreciated. However, correlation between triple negativity and CD44(+)/CD24(-/low) with tumor recurrence remains elusive. In the present study, we evaluated tumor specimens of 50 breast cancer patients with known hormone receptor status for whom we had follow-up information and outcome data available, and performed immunohistochemistry analysis to determine CD44 and CD24 expression. Gene expression arrays were also independently performed on 52 breast cancer specimens with banked frozen tissue. Lastly, we used FVBN202 transgenic mouse model of breast carcinoma and determined the hormone receptor status, the proportion of CD44(+)/CD24(-/low) breast cancer stem-like cells, and the behavior of the tumor. We determined that patients with triple-negative tumors had significantly higher incidence of recurrence or distant metastasis associated with increased frequency of breast cancer stem cell phenotypes compared with those with non-triple-negative tumors. Preclinical studies in FVBN202 transgenic mice confirmed these findings by showing that relapsed tumors were triple negative and had significantly higher frequency of breast cancer stem cells compared with their related primary tumors. Unlike non-triple-negative primary tumors, relapsed triple-negative tumors were tumorigenic at low doses when inoculated into FVBN202 transgenic mice. These findings suggest that CD44(+)/CD24(-/low) breast cancer stem-like cells play an important role in the clinical behavior of triple-negative breast cancer and that development of therapeutic targets directed to breast cancer stem-like cells may lead to reduction in the aggressiveness of triple-negative breast cancers.
authors.affiliation: Department of Pathology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA. midowu@vcu.edu
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.forename: Maciej
authors.initials: M
authors.lastname: Kmieciak
authors.forename: Catherine
authors.initials: C
authors.lastname: Dumur
authors.forename: Regina S
authors.initials: RS
authors.lastname: Burton
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Grimes
authors.forename: Celeste N
authors.initials: CN
authors.lastname: Powers
authors.forename: Masoud H
authors.initials: MH
authors.lastname: Manjili
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011987:Receptors, Steroid; C497889:CD24 protein, human; C497483:CD44 protein, human