Claudin expression in breast cancer: High or low, what to expect?
Sara Ricardo1,2, Renê Gerhard1, Jorge F. Cameselle-Teijeiro3, Fernando Schmitt1,4 and Joana Paredes1,4
1IPATIMUP, Institute of Molecular Pathology and Immunology of Porto University, Porto, Portugal, 2ICBAS – Abel Salazar Biomedical Sciences Institute, Porto, Portugal, 3Complexo Hospitalar Universitario de Vigo (CHUVI), Vigo, Spain and 4Medical Faculty of Porto University, Porto, Portugal
Offprint requests to: Joana Paredes, IPATIMUP, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal. e-mail: jparedes@ipatimup.pt
Summary. The evaluation of claudins (CLDNs) expression pattern in tumours can be important to understand breast carcinogenesis. The study of CLDNs became more appealing since it was found that CLDN3 and CLDN4 are putative therapeutic targets for Clostridium perfrigens enterotoxin (CPE), as well as for monoclonal antibody-based therapy. Moreover, the recently characterized CLDN-low molecular subgroup of breast tumours increased the interest in these molecules. Based on these facts, our aim was to explore the pattern of expression of CLDNs among a large series of invasive breast carcinomas. We also analysed the correlation between the combinatorial expression of CLDN3/CLDN4 and classical prognostic factors and biological markers. In addition, we also compared the characteristics of tumours with low expression of CLDN3, CLDN4 and CLDN7, assessed by immunohistochemistry (IHC), and the ones from CLDN-low subgroup of tumours previously defined by genomic assays.
The combinatorial analysis of the expression of CLDN3/CLDN4 showed a significant association between high CLDN3/CLDN4 levels and triple-negative tumours, as well as with worse patient outcome. This combined analysis may provide useful information for breast carcinomas, since these two CLDN members are putative therapeutic targets. Comparing tumours with low expression of CLDN3, CLDN4 and CLDN7 with tumours previously referred to as CLDN-low by genomic assays, we demonstrated that the single IHC evaluation of these three specific CLDNs is insufficient to identify the CLDN-low molecular subtype of breast tumours. The analysis of several other molecular markers, such as EMT (epithelial-to-mesenchymal transition) and CSC (cancer stem cell) markers should probably be added to improve the identification of this subgroup of tumours by IHC, which probably are enriched in carcinomas with metaplastic differentiation. Histol Histopathol 27, 1283-1295 (2012)
Key words: Claudin-1, Claudin-3, Claudin-4, Claudin-7, Breast cancer molecular subtype
DOI: 10.14670/HH-27.1283