Expression of Desmogleins in Paget Cells of Mammary and Extramammary Paget's Disease

Abstract

Sagebiel (1969) electronmicroscopically observed that desmosomes are present between adjacent Paget cells, as well as between Paget cells and adjacent keratinizing epidermal cells. Desmosomes contain the proteins desmoglein (Dsg) and desmocollin as their transmembrane components, and Dsg has three isotypes. Among the three isotypes of Dsg, Dsg1 and Dsg3 are autoantigens for pemphigus foliaceus and pemphigus vulgaris (PV), respectively. We examined the expression of Dsgs in Paget cells of mammary and extramammary Paget's disease. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 with extramammary Paget's disease. One part of the samples was cut into small pieces and epidermal sheets were separated with dispase, then treated with a mixture of EDTA and trypsin. The resulting cell suspensions were cultured in low Ca⁺⁺ medium, then the cells were incubated in high Ca⁺⁺ medium. Paget cells identified with anti-epithelial membrane antigen (EMA) antibody were positive for serum from a PV patient which was confirmed to react with both Dsg1 and Dsg3. However, the intensity of fluorescence of Paget cells was weaker than that of EMA-negative keratinocytes. In the cryostat sections, Paget cells identified with anti-EMA antibody showed the same staining pattern as cultured cells in high Ca⁺⁺ medium. The data presented in this study confirm that Paget cells express Dsgs, and are consistent with the electronmicroscopical data by Sagebiel (1969). However, our data do not support the hypothesis that Paget cells are of keratinocyte origin, because sweat ducts or sweat glands could be positive for sera from PV patients. It is necessary to confirm whether or not sweat ducts or sweat glands express Dsgs, because sera from PV patients exhibit high background in the dermis.