P2-01-18: Cancer Stem-Like Cells in Breast Cancer Progression.

Abstract

Abstract Background: increasing evidences support the presence of cancer stem-like cells (CSLCs) within breast carcinomas. A subset of cells enriched for CSLCs within the tumor can be identified by flow cytometry. It has been supposed that CSLC component is responsible for tumor resistance and metastasis. However, the analysis of such population has never been evaluated during breast cancer progression. Patients and Methods: We prospectively included 98 women with histologically proven breast carcinomas to assess the presence of CSLCs within the primary tumor. According to clinical stage (CS), five patients were CS 0 (palpable DCIS), 16 CS I, 20 CS II and negative lymph nodes (IIA-), 20 CS II and positive lymph nodes (IIA+), 6 IIIa, 17 IIIb, 1IIIc and 2 CS IV. Additionally, ten lymph node metastases from IIA+ patients were analyzed. Invasive ductal carcinoma (IDC) was observed in 79 patients. We excluded from the analysis patients with non ductal histology (n= 11). The percentage of CD44+/CD24- (n= 79), ALDH1+ (ALDEFLUOR®) (n= 29), ABCG2+ (n= 44) and CXCR4+ (n= 46) cells within ESA+ cells was determined by flow cytometry in fresh sampled tumors. The mammosphere assay was studied in 14 samples. The relationship between cytometry analyses and clinical and pathological features was analyzed. Results: The median prevalence of CD44+/CD24- cells within ESA+ population was 1.63% in stage 0, 2.39% in stage I, 0.42% in stage IIA-, 8.15% in stage IIA+, 0.52% in stage III (p=0.005). The CD44+/CD24- cell population was analyzed in 10 lymph node metastasis and, the median prevalence of this population within ESA+ cells was 4.7%. There was no variation of median prevalence of ALDH1+, CXCR4+, ABCG2+ and the median number of spheres among clinical stages (p=0.1, p=0.8, p=0.8, p=0.8, respectively). We didn't observe any association among the expression of, ABCG2+, CXCR4+ with histological grade and the expression of ER and PgR. The median percentage of CD44+/CD24- cells was higher (2.39% vs 0.41%) in ER positive tumors (p=0.003). The median percentage of ESA+/ CXCR4+ cells was higher (42,5% vs 9,7%) in HER2− tumors. There was no correlation between the studied markers and the patients’ age and clinical tumor diameter. The results are summarized in Table 1. Results of association between expression cells surface markers and ALDH1 activity (Aldefluor®) with clinical and pathological features in invasive ductal carcinomas. Discussion: We found a significant variation in CSLC population during breast cancer progression. Our data show a gradual increase in CD44+/CD24- cells within ESA+ population from stage 0 to stage IIA+ and a significant decrease in stage III tumors. This observation supports the hypothesis that a population of CSLCs could be associated with breast cancer progression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-18.