Immunohistochemical localization of transforming growth factor-alpha and epithelial growth factor receptor in human fetal developing skin, psoriasis and restrictive dermopathy.

Keratinocytes release a number of cytokines interacting with other intra- and subepidermal cells during the initiation and the perpetuation of skin inflammatory reactions. Cultured human keratinocytes overexpressing the transforming growth factor alpha (TGF-alpha) assumed a spindled morphology and displayed increased locomotion. Moreover, the receptor for TGF-alpha, the epithelial growth factor receptor (EGFR), is important for autocrine growth, promotion of cell survival, and regulation of cell migration. The expression of TGF-alpha and EGFR has not been widely studied in human developing skin and their roles in geno-dermatosis are not known. In this study, we investigated the expression of TGF-alpha and EGFR by immunohistochemistry in human developing skin at different gestational ages (14 th week, 20 th week, and 34 th week), in six patients with psoriasis, and, for the first time, in an infant affected with restrictive dermopathy, a very rare lethal genodermatosis, characterized by abnormal skin growth and differentiation with thin, tightly adherent skin. TGF-alpha and EGFR were expressed in the basal layer at the 14 th week and in all epidermal layers at the 20 th and 34 th week of gestation. In psoriasis, TGF-alpha was overexpressed in all layers of epidermis, while EGFR was expressed in the basal and first suprabasal layers. In restrictive dermopathy, we observed no expression of both TGF-alpha and EGFR at the level of the skin. The other organs showed comparable patterns to those of an age-matched infant. In conclusion, TGF-alpha and EGFR interact strictly to promote skin development during the intrauterine life. An interactive autocrine growth cycle between TGF-alpha and EGFR is present in psoriasis. A skin-localized alteration of the expression of TGF-alpha and EGFR may be at the basis of restrictive dermopathy. The delay of growth and differentiation of the skin in restrictive dermopathy may be related to the absent expression of TGF-alpha, which is probably due to a down regulation of EGFR by an abnormal autocrine mechanism.