In normal skin, cytokeratin polypeptides are expressed in different cell-type-specific patterns, in the keratinocytes of the different epidermal cell strata as well as in different lateral epithelial domains. Using light microscopically controlled microdissection of defined regions from frozen sections of biopsies, we have prepared cytoskeletons of various benign and malignant keratinocyte-derived tumors of human skin and analyzed their cytokeratin polypeptide patterns by two-dimensional gel electrophoresis. Premalignant fibroepitheliomas and basal cell epitheliomas display a relatively simple cytokeratin pattern (cytokeratins nos. 5, 14, 15, and 17). Pseudocarcinomatous hyperplasia, some squamous cell carcinomas, and a certain subtype of condylomata acuminata present a hair-follicle-like pattern (nos. 5, 6, 14, 16, 17). In addition to these components, variable, mostly low amounts of cytokeratins nos. 1 (Mr 68,000), and 11 are detected in most squamous cell carcinomas, in keratoacanthomas, verruca vulgaris, and another type of condylomata acuminata. In molluscum contagiosum, verruca plana, solar keratosis, and seborrheic keratosis, the cytokeratin expression is shifted more towards the normal epidermal pattern (polypeptides nos. 1, 2, 5, 10, 11, 14, 15 and traces of nos. 6 and 16 in the latter two tumors). No tumor-specific cytokeratins have been found. We conclude that keratinocyte-derived skin tumors contain various combinations of cytokeratins of the subset typical for normal keratinocytes of skin, but no cytokeratins typical for internal, simple epithelia. Different groups of tumors can be distinguished by their specific cytokeratin patterns. Possible applications of cytokeratin typing in clinical diagnosis are discussed.
