Arnaud DA Cruz Paula1, Oriana Marques2, Rita Sampaio3, Ana Rosa4, José Garcia3, Alexandra Rêma5, Maria DE Fátima Faria5, Paula Silva6, Ramón Vizcaíno3, Carlos Lopes1. 1. Pathology and Molecular Immunology Department, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal Department of Pathology, Portuguese Oncology Institute, Porto, Portugal arnaudcpaula@hotmail.com calopes@icbas.up.pt. 2. Pathology and Molecular Immunology Department, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal Unit for Multidisciplinary Biomedical Research, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal Basic and Clinical Research on Iron Biology, Institute of Molecular and Cell Biology/i3S, Porto, Portugal. 3. Department of Pathology, Porto Hospital Centre, Porto, Portugal. 4. Pathology and Molecular Immunology Department, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal Basic and Clinical Research on Iron Biology, Institute of Molecular and Cell Biology/i3S, Porto, Portugal. 5. Pathology and Molecular Immunology Department, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal. 6. Faculty of Medicine, University of Porto, Porto, Portugal Science Diffusion, Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
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. Copyright
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. Copyright
Authors: Arnaud Da Cruz Paula; Catarina Leitão; Oriana Marques; Ana Margarida Rosa; Ana Helena Santos; Alexandra Rêma; Maria de Fátima Faria; Ana Rocha; José Luís Costa; Margarida Lima; Carlos Lopes Journal: Virchows Arch Date: 2017-01-23 Impact factor: 4.064
Authors: Olga E Savelieva; Liubov A Tashireva; Evgeniya V Kaigorodova; Angelina V Buzenkova; Rustam Kh Mukhamedzhanov; Evgeniya S Grigoryeva; Marina V Zavyalova; Natalia A Tarabanovskaya; Nadezhda V Cherdyntseva; Vladimir M Perelmuter Journal: Int J Mol Sci Date: 2020-04-16 Impact factor: 5.923