Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells. Utilizing in vitro and in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties. These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model. In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor. In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis. These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.

The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.

Purpose: To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer.Experimental Design: CSCs were isolated from SUM149 and MARY-X, an IBC cell line and primary xenograft, by virtue of increased aldehyde dehydrogenase (ALDH) activity as assessed by the ALDEFLUOR assay. Invasion and metastasis of CSC populations were assessed by in vitro and mouse xenograft assays. Expression of ALDH1 was determined on a retrospective series of 109 IBC patients and this was correlated with histoclinical data. All statistical tests were two sided. Log-rank tests using Kaplan-Meier analysis were used to determine the correlation of ALDH1 expression with development of metastasis and patient outcome.Results: Both in vitro and xenograft assays showed that invasion and metastasis in IBC are mediated by a cellular component that displays ALDH activity. Furthermore, expression of ALDH1 in IBC was an independent predictive factor for early metastasis and decreased survival in this patient population.Conclusions: These results suggest that the metastatic, aggressive behavior of IBC may be mediated by a CSC component that displays ALDH enzymatic activity. ALDH1 expression represents the first independent prognostic marker to predict metastasis and poor patient outcome in IBC. The results illustrate how stem cell research can translate into clinical practice in the IBC field. Clin Cancer Res; 16(1); 45-55. ©2010 AACR.Inflammatory breast cancer (IBC) is an angioinvasive form of breast cancer associated with a high incidence of early nodal and systemic metastasis. In contrast to the recent decrease in breast cancer incidence in the United States, the annual incidence of IBC continues to increase (1, 2) with an attendant increase in mortality (3). Despite advances in the use of systemic chemotherapy, the prognosis of IBC remains considerably worse than that of other locally advanced breast cancers (1).Several molecular changes have been described in IBC including RHOC overexpression, hypomethylation of caveolin-1 or caveolin-2 promoters, and deletion of the tumor suppressor WISP3 (4-8). In addition, IBCs have been reported to overexpress E-cadherin/α, β-catenin, and angiogenic factors (4,7,(9)(10)(11)(12)(13)(14). Although each of these genetic changes may contribute to the metastatic nature of IBC, no markers have been described that can predict the development of systemic metastasis or survival in IBC patients. Although ERBB2 expression is associated with aggressive behavior in most breast cancers, this is not the case in IBC (15).There is increasing evidence that human breast cancers are driven by a tumor-initiating "cancer stem cell" (CSC) component that may contribute to tumor metastasis and therapeutic resistance (16)(17)(18)(19)(20). Breast CSCs were initially characterized as CD44 + /CD24 − /lin − cells that were capable of serial transplantation in nonobese/severe combined immunodefic...

International audienceA better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression pro. ling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on `cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published `intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management