Prostaglandin-H-synthase isozyme expression in normal and neoplastic humanskin

Expression of prostaglandin-H-synthase (PGHS) isozymes was analyzed in 50 b iopsies of normal human skin and of pre-malignant and malignant skin lesion s, by means of quantitative RT-PCR, immunoprecipitation and Western blottin g, as well as immunohistochemistry. Normal skin constitutively expressed PG HS-1 in all cell layers of the epidermis, in endothelial cells of small blo od vessels and in sweat-gland epithelium. PGHS-2 expression was very low an d restricted to a few keratinocytes of the interfollicular and follicular e pidermis, Steady-state concentrations of PGHS-1 and PGHS-2 mRNA were simila r in normal skin and in basal-cell carcinomas, but PGHS-1 mRNA was reduced and PGHS-2 mRNA was elevated in actinic keratoses, squamous-cell carcinomas and keratoacanthomas. PGHS-1 protein was detected in all tumor biopsies, b eing occasionally increased in basal-cell carcinomas. High amounts of PGHS- 2 protein were found in actinic keratoses, squamous-cell carcinomas and ker atoacanthomas, but not in basal-cell carcinomas. Four malignant melanomas i ncluded in this study contained PGHS-1 but no PGHS-2 protein. Immunohistoch emical analysis of the biopsies identified keratinocytes, in addition to ce lls of inflammatory infiltrates and of dendritic morphology, as the major P GHS-expressing cell types. PGHS-2-specific signals were spread throughout t he epidermal part of actinic keratoses and squamous-cell carcinomas. These data suggest that constitutive up-regulation of PGHS-2 expression is a cons istent pre-malignant event in squamous-cell cancer development in man, as i t is in animal models of skin carcinogenesis. Thus, pre-cancerous lesions s uch as actinic keratoses present a likely target for chemoprevention of ski n cancer by selective PGHS-2 inhibitors. Int. J. Cancer 82:648-656, 1999. ( C) 1999 Wiley-Liss, Inc.