Immunohistochemical localization of members of the transforming growth factor (TGF)-β superfamily in normal human salivary glands and pleomorphic adenomas

: Although pleomorphic adenoma is the most common type of salivary gland epithelial tumor, it frequently contains “mesenchymal”‐like components, including myxoid or chondroid tissues. We reported previously that chondroid tissue formation in pleomorphic adenoma was associated with overexpression of bone morphogenetic proteins (BMPs) by neoplastic myoepithelial cells. BMPs belong to the transforming growth factor (TGF)‐β superfamily, so we hypothesized that pleomorphic adenoma may express TGF‐βs and that these molecules may regulate mesenchymal‐like tissue formation. To evaluate this hypothesis, we immunohistochemically examined TGF‐β1, ‐β2 and ‐β3 expression and localization in normal salivary glands and in 43 cases of pleomorphic adenomas. There was no evidence of TGF‐β1 expression in normal salivary glands or pleomorphic adenomas. Signals for TGF‐β2 in the normal salivary glands were observed in the intercalated ducts, while in pleomorphic adenomas they were observed in the inner ductal cells of the tubulo‐glandular structures. Signals for TGF‐β3 in the normal salivary glands were observed in mucous cells, whereas in pleomorphic adenomas they were observed in the solid nests of neoplastic myoepithelial cells, in the portion showing squamous metaplasia, and in the inner ductal cells of tubulo‐glandular structures. TGF‐βs induce ectopic cartilage formation in vivo, but chondroid tissues in pleomorphic adenomas showed only weak TGF‐β3 expression. TGF‐β may be related to differentiation of the inner ductal cells and the neoplastic myoepithelial cells. In conclusion, pleomorphic adenomas expressed TGF‐β2 and ‐β3, which may be associated with differentiation of the inner ductal cells and neoplastic myoepithelial cells.