DYSREGULATED EXPRESSION OF TRANSFORMING-GROWTH-FACTOR-BETA AND ITS TYPE-I AND TYPE-II RECEPTORS IN BASAL-CELL CARCINOMA

In mammals, transforming growth factor-beta (TGF-beta) is found in 3 h ighly homologous isoforms that exert their effects via heteromeric com plexes of type-I and type-ii receptors (T beta R-I and T beta R-II). T GF-beta regulates the growth and metabolism of various cell types, inc luding keratinocytes. We have investigated the immunohistological loca lization of TGF-beta 1, TGF-beta 2, T beta R-I and T beta R-II in norm al human skin, basal-cell carcinoma (BCC), Bowen's disease, seborrheic keratosis, eccrine poroma and eccrine spiradenoma using frozen tissue specimens. In normal human skin, the immunoreactive TGF-beta 2, but n ot TGF-beta 1, was detected predominantly in the epidermis, follicles and sebaceous glands. The epidermal expression of T beta R-I and T bet a R-II was very weak in the majority of normal skins. In BCC, TGF-beta 2 expression was markedly reduced or completely negative. In addition , T beta R-I- and T beta R-II-positive stromal cells were accumulated in the fibrotic stroma in some BCCs. These stromal cells were partly b ut moderately positive for TGF-beta I. Decreased expression of TGF-bet a 2 was likely to be associated with the differentiation state of BCC cells, since TGF-beta 2 expression was clearly observed in the squamoi d foci of BCC. In addition, no expression of TGF-beta 2 was detected i n the eccrine secretory portion or in eccrine spiradenoma, but it was detected in the upper eccrine ducts and in eccrine poroma. (C) 1997 Wi ley-Liss, Inc.