RT Journal Article SR Electronic T1 Characterization of CD44+ALDH1+Ki-67 Cells in Non-malignant and Neoplastic Lesions of the Breast JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4629 OP 4638 VO 36 IS 9 A1 ARNAUD DA CRUZ PAULA A1 ORIANA MARQUES A1 RITA SAMPAIO A1 ANA ROSA A1 JOSÉ GARCIA A1 ALEXANDRA RÊMA A1 MARIA DE FÁTIMA FARIA A1 PAULA SILVA A1 RAMÓN VIZCAÍNO A1 CARLOS LOPES YR 2016 UL http://ar.iiarjournals.org/content/36/9/4629.abstract AB 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.