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.

Impact of the surgeon on the prevalence of arteriovenous fistulas.

Decreased use of native arteriovenous fistulas and an increased reliance on synthetic grafts as permanent dialysis access have accompanied the growth of the dialysis population in the United States, but not at our institution. Possible reasons for this difference were studied in a cross-sectional analysis in August of 2000. There were 51 chronic dialysis patients, all of whom had their access placed by the same surgeon; 75% of them were dialyzed through an arteriovenous fistula, which compares well with the 23% prevalence at the national level. Among our patients, 57% were diabetic, 98% had a history of hypertension, 35% had amputations or arterial bypass surgery, 37% had coronary artery disease, 12% had suffered a stroke, 35% were active smokers, and 22% had a history of intravenous drug use. The high prevalence of arteriovenous fistulas, despite so many comorbid conditions, suggests that the presence of a skilled and experienced surgeon may be more predictive of better dialysis access than other factors.