Dysregulated expression of transforming growth factor β and its type-I and type-II receptors in basal-cell carcinoma

In mammals, transforming growth factor-β (TGF-β) is found in 3 highly homologous isoforms that exert their effects via heteromeric complexes of type-I and type-II receptors (TβR-I and TβR-II). TGF-β regulates the growth and metabolism of various cell types, including keratinocytes. We have investigated the immunohistological localization of TGF-β1, TGF-β2, TβR-I and TβR-II in normal 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-β2, but not TGF-β1, was detected predominantly in the epidermis, follicles and sebaceous glands. The epidermal expression of TβR-I and TβR-II was very weak in the majority of normal skins. In BCC, TGF-β2 expression was markedly reduced or completely negative. In addition, TβR-I- and TβR-II positive stromal cells were accumulated in the fibrotic stroma in some BCCs. These stromal cells were partly but moderately positive for TGF-β1. Decreased expression of TGF-β2 was likely to be associated with the differentiation state of BCC cells, since TGF-β2 expression was clearly observed in the squamoid foci of BCC. In addition, no expression of TGF-β2 was detected in the eccrine secretory portion or in eccrine spiradenoma, but it was detected in the upper eccrine ducts and in eccrine poroma.