The patterns of expression of cytokeratin polypeptides which are closely correlated to routes of differentiation of epithelial cells were studied in extramammary Paget's disease. Cytokeratins of uninvolved and involved epidermis were analyzed by two-dimensional gel electrophoresis of microdissected tissue preparations as well as by immunofluorescence microscopy using cytokeratin antibodies with different specificities. In uninvolved epidermis, cytokeratins Nos. 1, 5, 6, 10, 11, 14, and 16, characteristic of keratinocytes, were found. Epidermis infiltrated by Paget's cells contained the same components and, in addition, cytokeratins Nos. 7, 8, 18, and 19, the latter being characteristic of simple and glandular epithelia, including apocrine and eccrine skin glands. By immunohistochemistry, broad-spectrum antibodies to cytokeratins decorated both keratinocytes and Paget's cells. Antibodies selective for cytokeratins Nos. 1, 10, and 11 stained suprabasal keratinocytes but not Paget's cells. In contrast, antibodies to cytokeratin No. 18 were negative on keratinocytes but the Paget's cells were selectively stained, as were the secretory cells but not the ductal cells in apocrine and eccrine glands. The results show that the cytoskeleton of Paget's cells is different from that of keratinocytes and ductal cells of skin glands and suggest that these tumor cells express the glandular type cytokeratins Nos. 7, 8, 18, and 19. This provides cell biologic support for a relationship of cells of Paget's disease to secretory cells of apocrine and eccrine glands. The histogenesis of extramammary Paget's cells is discussed in relation to these findings.
