Immature and mature dendritic cells in mammary Paget's disease.

T Brunhuber, MDa, C Ensinger, MDa, G Mikuz, MDa, N Romani, PhDb, S Saeland, PhDc, S Lebecque, PhDc, P Obrist, MDa

aDepartment of Pathology, University of Innsbruck Medical School, Innsbruck, Austria, bDepartment of Dermatology, University of Innsbruck Medical School, Innsbruck, Austria, cSchering-Plough Laboratory for Immunological Research, Dardilly, France

Aim: In the course of our study we tried to investigate the composition of the prominent tumour-accompanying inflammatory infiltrate in patients with intraepidermally spreading adenocarcinoma of the breast with special emphasis to immature and mature dendritic cells and their distributional pattern in Mammary Paget's disease. Methods: Immunhistochemical investigations with antibodies against CD1a, S-100, as well as novel reagents against Langerin/CD207 DC-LAMP/CD208 and p55 (Fascin) were performed on paraffin-embedded samples of Mammary Paget's disease (n=27) and of disease-free nipple skin (n=10). Additionally, double-labeling experiments with antibodies against S-100 and the Paget-specific cytokeratin CK-7 were conducted. Results: In comparison to disease-free samples we found an marked increase in the numbers and a prominent shift in the distribution of immature and mature dendritic cells in Paget cell-infiltrated mamillary tissue. CD1a+ immature dendritic cells were concentrated in the Paget lesion itself. Langerin+ dendritic cells of the Langerhans cell type appeared to be attracted into the peripheral parts of the tumour-infiltrated epidermis whereas the centre of the lesion was almost free of Langerhans cells. DC-LAMP+ and p55+ mature dendritic cells could be detected in the accompanying inflammatory reaction beneath the Paget cell-infiltrated squamous epithelium intermixed with T and B lymphocytes as well as Natural Killer cells. S-100+ dendritic cells with CK-7+ material stored in their cytoplasm could be shown in both the Paget lesion and the infiltrate below. Conclusions: Our findings may indicate that dendritic cells play an important part in an effective ongoing-anti-tumour immune response in this special variant of breast cancer.

KEY WORDS: Breast cancer, Langerhans' cells, immunohistochemistry.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Immunotherapy.