TY - JOUR T1 - Characterization of CD44<sup>+</sup>ALDH1<sup>+</sup>Ki-67<sup>−</sup> Cells in Non-malignant and Neoplastic Lesions of the Breast JF - Anticancer Research JO - Anticancer Res SP - 4629 LP - 4638 VL - 36 IS - 9 AU - ARNAUD DA CRUZ PAULA AU - ORIANA MARQUES AU - RITA SAMPAIO AU - ANA ROSA AU - JOSÉ GARCIA AU - ALEXANDRA RÊMA AU - MARIA DE FÁTIMA FARIA AU - PAULA SILVA AU - RAMÓN VIZCAÍNO AU - CARLOS LOPES Y1 - 2016/09/01 UR - http://ar.iiarjournals.org/content/36/9/4629.abstract N2 - Background: Cancer stem cells are tumor cells that present self-renewal, clonal tumor initiation capacity and clonal long-term repopulation potential. We have previously demonstrated that the co-expression of the breast cancer stem cell (BCSC) markers hyaluronan receptor (CD44) and aldehyde dehydrogenase-1 (ALDH1) in ductal carcinomas in situ could be determinant for disease progression. Combining these established BCSC markers with Ki-67 to evaluate quiescence we sought to identify, evaluate the distribution and estimate the mean percentages of CD44+ALDH1+Ki-67− breast cells. Materials and Methods: Triple-immunohistochemistry for CD44, ALDH1 and Ki-67 was applied in a series of 16 normal, 54 non-malignant and 155 malignant breast tissues. Clinical relevance was inferred by associations with markers of breast cancer behavior, progression and survival. Results: The mean percentages of cells with this phenotype increased significantly from non-malignant lesions to high-grade ductal carcinomas in situ, decreasing in invasive ductal carcinomas, as also evidenced by an inverse correlation with histological grade and tumor size. The mean percentage of CD44+ALDH1+Ki-67− cells was also significantly higher in women who developed distant metastasis and died due to breast cancer, and a significant association with human epidermal growth factor type 2 (HER2) negativity was observed. Conclusion: Our novel findings indicate that CD44+ALDH1+Ki-67− tumor cells may favor distant metastasis and can predict overall survival in patients with ductal carcinomas of the breast. More importantly, quiescence may have a crucial role for tumor progression, treatment resistance and metastatic ability of BCSCs. ER -