Immunohistochemical tracking of an immune response in mammary Paget's disease.

Dendritic cells (DC) are the most potent antigen-presenting cells of the organism. They are specialized to capture, process, and present antigen via the MHC class II as well as the MHC class I pathways to CD4+ and CD8+ T cells, respectively. This results in T cell-mediated immune responses that are likely to counteract the generation and propagation of tumors in vivo. Therefore, we studied the distribution of dendritic cells in mammary Paget's disease. Paraffin-embedded samples of Paget's disease of the breast (n=27) and of disease-free epidermis of the nipple (n=10) were investigated immunohistochemically for the presence of dendritic cells, in particular of Langerhans cells, using antibodies against S-100, CD1a, and HLA-DR, as well as novel reagents against Langerin/CD207, DC-LAMP/CD208 and p55 (Fascin), the latter two being specific for mature dendritic cells. Paget samples presented a decrease of CD1a+, S-100+, and Langerin+ intraepidermal Langerhans cells in almost all cases. This was paralleled by a concentration of immature dendritic cells in the tumor-infiltrated tissue itself. Similar to infiltrating breast carcinoma we observed a marked increase of DC-LAMP+ and p55+ mature dendritic cells in the corial tissue beneath the tumor. These cells were almost always found in ribbon-like or nodular lymphocytic infiltrates. Moreover, rare mature dendritic cells were also found in the Paget cell-infiltrated epidermis of the nipple, i.e. in the tumorous lesion itself. These findings may indicate an effective ongoing anti-tumor immune response in this part of spreading breast cancer.