Abstract LB-106: Expression of stem cell biomarkers in benign breast tissue from patients with triple negative breast cancer

Abstract

Abstract Numerous studies suggest that breast cancers contain a subpopulation of cancer stem cells that are thought to maintain the heterogeneity and self-renewing potential of the tumor. In our previously published data, we had described a breast cancer stem cell signature comprised of 493 statistically significant differentially expressed genes, which were present in a tumorigenic subpopulation of cells. Cells from patient samples with the cell surface markers CD44+CD49f+CD133/2+ have been shown to have self-renewal and tumorigenic properties – characteristics of breast cancer stem cells. In this study, we investigated the benign tissue from 42 patients with breast cancer treated with mastectomy to examine the incidence CD44+CD49f+CD133/2+ positive cells. Benign tissue was obtained at a distant site, at least 5 cm from the primary tumor, and examined with hematoxylin-eosin by a breast pathologist (AS), only samples containing normal breast tissue with at least 60% epithelial content were selected. A significant increase in expression of CD44+CD49f+CD133/2+ by immunofluorescence was identified in the benign tissue associated with patients with triple negative (ER negative/PR negative/Her2 negative) disease (8 out of 8), compared with ER positive and Her2 positive tumors combined (5 out of 36), P<0.001, Wilcoxon rank sum test. The definition of a positive score was more then 1% positive staining or negative for less then 1% triple positive cells, scoring approximately 1000 cells per sample. We further examined whether global RNA expression from these benign tissues correlated to our previously published tumorigenic microarray signature. We found that array data from benign tissue from patients with triple negative breast cancer was significantly correlated with our previously published tumorigenic signature (P=.01 two sided t test). Thus, these pathologically defined benign cells bearing cancer stem cell markers may be cells of origin for tumor development in triple negative breast cancer, and their presence in benign tissue (including tissue in some cases from the uninvolved contralateral breast) implies a systemic etiology to triple negative breast cancer. In conclusion, putative cancer stem cell markers are enriched in the benign breast tissue of women who have developed triple negative breast cancer, and their presence may represent a biomarker for increased breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-106. doi:10.1158/1538-7445.AM2011-LB-106