Abstract
Purpose
Epithelial mesenchymal transition is a major mechanism to explain metastatic events in breast cancer. Another important aspect is that cells with stem cell properties are able to become resistant against chemotherapeutics. Our main goal was to investigate the role of the EMT marker, N-cadherin, and of the stem cell marker, CD133, in breast cancer.
Methods
The expressions of N-cadherin and CD133 were assessed by immunohistochemistry in 307 primary tumors from breast cancer patients and for 30 patients, in the related recurrences and/or metastases. We studied the correlation between both markers, their associations with known clinicopathological parameters and their role as predictive markers for survival time. Different expressions of both markers in primary tumor and recurrences or metastases were examined.
Results
N-cadherin and CD133 expressions correlated positively in the 261 primary tumor samples (p = 0.000) and in the 45 primary tumor, recurrence or metastasis samples (p = 0.010). In patients without lymph node metastases, the 10-year survival time was significantly lower when the tumor was N-cadherin-positive (p = 0.042). Expression of N-cadherin was also significantly higher in metastases than in the related primary tumors (p = 0.039).
Conclusion
N-cadherin and CD133 expressions are strongly correlated and N-cadherin appears as a potential metastases marker in a specific patient subpopulation.
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Abbreviations
- CSC:
-
Cancer stem cell
- DAB:
-
3, 3′-Diaminobenzidine
- EMT:
-
Epithelial to mesenchymal transition
- ERα:
-
Estrogen receptor α
- FGFR:
-
Fibroblast growth factor receptor)
- HER2:
-
Human epidermal growth factor receptor 2
- IRS:
-
Immunoreactive score
- MET:
-
Mesenchymal to epithelial transition
- MMP:
-
Matrix metalloproteinase
- PBS:
-
Phosphate buffered saline
- PI(3)K:
-
Phosphatidylinositide 3-kinase
- PR:
-
Progesterone receptor
- TNM classification:
-
Tumor-node-metastasis classification
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Acknowledgments
Thanks are due to Sandra Schulze for assistance in the protocol optimization and to Christoph Freier for assistance in creating the scatter blots.
Conflict of interest
The authors declare that they have no competing interests. We confirm that the authors have full control of all primary data and agree that the journal is allowed to review these data if requested.
Ethical standards
The study has been approved by the Ethical Committee of the Ludwig Maximilians University of Munich, Germany (LMU, ethical number 048-08) and has been carried out in concordance with the guidelines of the Helsinki Declaration. Written informed consent was obtained from the patients.
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Sophie Doisneau-Sixou and Udo Jeschke are co-last authors of this work.
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Bock, C., Kuhn, C., Ditsch, N. et al. Strong correlation between N-cadherin and CD133 in breast cancer: role of both markers in metastatic events. J Cancer Res Clin Oncol 140, 1873–1881 (2014). https://doi.org/10.1007/s00432-014-1750-z
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DOI: https://doi.org/10.1007/s00432-014-1750-z