Abstract
In the present study we investigated the protein expression of claudins 1, 3, and 4 and their relationship to clinical variables and outcome in a cohort of ER−ve and ER+ve human invasive breast cancers. Immunohistochemical analysis was performed on tissue microarrays representing a total of 412 tumors and interpretable data was derived from 314, 299, and 306 tumors for claudins 1, 3, and 4, respectively. In the ER+ve subset, 5%, 89%, and 52%, and in the ER−ve subset, 39%, 79%, and 79% of tumors stained positively for claudins 1, 3, and 4, respectively (p < 0.0001, p = 0.026, p < 0.0001). Thus, in the two subsets, a significantly higher number of tumors were positive for claudins 3 and 4, compared to claudin 1. In addition, protein expressions of claudins 1 and 4 were significantly higher in those tumors that displayed characteristics of the basal-like subtype of breast cancers (ER−ve, Her-2−ve, EGFR+ve, CK5/6+ve). This study shows a unique pattern of expression for the different claudins in ER−ve and ER+ve tumors. Our data also suggests that increased expression of claudins 1 and 4 was associated with the basal-like subtype of breast cancers, a subtype generally linked to poor outcome.
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Abbreviations
- EGFR:
-
Epithelial derived growth factor receptor
- EMT:
-
Epithelial mesenchymal transition
- ER:
-
Estrogen receptor
- IHC:
-
Immunohistochemistry
- LBA:
-
Ligand-binding assay
- OS:
-
Overall survival
- RFS:
-
Relapse-free survival
- TMA:
-
Tissue microarray
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Acknowledgements
The authors would like to thank the personnel at the MBTB for technical support. GPS was funded by a Postdoctoral Fellowship from the Manitoba Health Research Council (MHRC) and previously from the CancerCare Manitoba Foundation (CCMF). TLY was formerly funded by a Manitoba Graduate Scholarship, and is currently funded by a Manitoba Health Research Council Studentship. YM is a Manitoba Medical Service Foundation Career Awardee. This study was supported by a grant from the Health Sciences Research Foundation. Biostatistical consultation was kindly provided by M. Cheang, Sr. Systems Analyst, Department of Community Health Sciences, Faculty of Medicine, University of Manitoba.
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The authors have no known conflicts of interests either financial or personal between themselves and others that might bias the work.
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Blanchard, A.A., Skliris, G.P., Watson, P.H. et al. Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates with markers of the basal phenotype. Virchows Arch 454, 647–656 (2009). https://doi.org/10.1007/s00428-009-0770-6
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DOI: https://doi.org/10.1007/s00428-009-0770-6