Simultaneous appearance of keratin modifications and γ-glutamyltransferase activity as indicators of tumor progression in mouse skin papillomas

γ-Glutamyltransferase (GGT), an enzyme not found in normal adult epidermis, was detected in most skin papillomas larger than 13 mm in diameter and in all squamous carcinomas induced by 7,12-dimethylbenz[a]anthracene initiation and 12-O-tetradecanoyl-phorbol 13-acetate promotion in noninbred Sencar mice. Furthermore, these GGT-positive lesions were also characterized by a marked decrease or absence of high-molecular-weight components of epidermal keratin. Since these characteristics are common to both carcinomas and large papillomas but are practically undetectable in normal epidermis and small papillomas, GGT activity and lack of high-molecular-weight keratin components seem to be good indicators of tumor progression, i.e., from papilloma to squamous carcinoma.