Overexpression of amphiregulin, a major autocrine growth factor for cultured human keratinocytes, in hyperproliferative skin diseases

Previous studies have indicated that amphiregulin is a major autocrine growth factor for cultured human keratinocytes. Its overexpression could therefore be important in hyperproliferative skin diseases. The purpose of this preliminary study was to determine if there is upregulation of amphiregulin protein in those disorders. A variety of lesions was surveyed for qualitative alterations in its immunostaining with an anti-amphiregulin monoclonal antibody. Amphiregulin was barely detectable in the epidermis of normal controls, although there was random nuclear staining of keratinocytes, and the epidermal appendages, especially sebaceous glands, were usually reactive. In contrast, psoriatic lesions exhibited prominent cytoplasmic staining of basal and spinous keratinocytes. Somewhat increased reactivity was also evident in actinic keratoses, in nests of squamous carcinoma cells, and in verrucae. Adnexal tumors were often strongly stained. Whereas basal cell carcinomas were nonreactive, staining was present in adjacent epidermis. Similarly, the melanocytes of nevi and melanoma were nonreactive but there was increased staining in contiguous keratinocytes. The pattern of amphiregulin immunostaining suggests a role for the protein in the aberrant keratinocyte growth of hyperproliferative disorders.