AN IMMUNOHISTOCHEMICAL AND HISTOCHEMICAL-STUDY OF CYTOKERATIN, INVOLUCRIN AND TRANSGLUTAMINASE IN SEBORRHEIC KERATOSIS

The mode of differentiation of seborrhoeic keratoses was investigated by immunohistochemical staining using cytokeratin (CK) polypeptide-spe cific monoclonal antibodies and an antibody specific for the particula te form of epidermal transglutaminase (ETgase), and by applying an ant i-human involucrin serum. The role played by (E)Tgase was further eval uated using an activity assay based on the covalent attachment of mono dansylcadaverine. Samples of uninvolved epidermis served as reference tissue. CK reactivities suggested that seborrhoeic keratoses is a hype rproliferative disease with an epidermal CK composition. CK5 and CK14 mere prominent markers of basal and basaloid keratinocytes, whereas a decrease in staining occurred in advanced maturation stages and areas of terminal keratinization. In contrast, CK1 and CK10 were prominent m arkers of suprabasaloid differentiation stages and produced complement ary stainings to those of CK5 and 14. Generally, CK10 staining was mor e impressive than CK1 staining and seemed to start before CK1 staining . In contrast to CK10 staining, cornified areas lost CK1 reactivity, T hese staining patterns were similar to those observed in uninvolved re ference tissues. The epidermal CK subset was further supplemented with the 'hyperproliferative' CK6 and 16 which occur sequentially, Positiv e staining for CK6 was noted from basal and proximal basaloid cells on wards, whereas distal basaloid cells additionally showed CK16 staining . The presence of other non-epidermal CK polypeptides could not be sho wn. The competence for other differentiation markers belonging to the group of (E)Tgase and cornifying cell membranes also evolved with a ty pical epidermal pattern. (E)Tgase activity was restricted to advanced and terminal stages of keratinization and was dual in nature, i.e. a d iffuse cytoplasmic staining occurred together with a prominent stainin g of cornifying cell membranes. Similarly, involucrin first detected i n the cytosol of distal basaloid cells, was soon translocated to the c ornifying cell membrane, reflecting its function as an ETgase substrat e and precursor of the marginal band. Finally, the immunolocalization of the particulate form of ETgase was strikingly similar to the locati on of the first two markers. Taken together, the results allow us to c onclude that seborrhoeic keratoses exhibits a hyperproliferative varia nt of the epidermal keratinization process, Maturation of basal kerati nocytes is greatly retarded leading to an accumulation of basaloid cel ls which retain the molecular markers of basal cells in proximal areas , but progressively gain the molecular markers of advancing maturation in distal areas.