@article {DA CRUZ PAULA4629, author = {ARNAUD DA CRUZ PAULA and ORIANA MARQUES and RITA SAMPAIO and ANA ROSA and JOS{\'E} GARCIA and ALEXANDRA R{\^E}MA and MARIA DE F{\'A}TIMA FARIA and PAULA SILVA and RAM{\'O}N VIZCA{\'I}NO and CARLOS LOPES}, title = {Characterization of CD44+ALDH1+Ki-67- Cells in Non-malignant and Neoplastic Lesions of the Breast}, volume = {36}, number = {9}, pages = {4629--4638}, year = {2016}, publisher = {International Institute of Anticancer Research}, abstract = {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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/36/9/4629}, eprint = {https://ar.iiarjournals.org/content/36/9/4629.full.pdf}, journal = {Anticancer Research} }