Immunohistochemical demonstration of bone morphogenetic protein-2 and type II collagen in pleomorphic adenoma of salivary glands.

Immunohistochemical investigation of bone morphogenetic protein-2 (BMP-2) and type II collagen, two cartilage-associated proteins, was undertaken using monoclonal antibodies in 20 cases of salivary pleomorphic adenoma (PA) in order to explore their possible roles in chondroid differentiation of this tumor. Other salivary gland tumors, including adenoid cystic carcinoma (17 cases), polymorphous low-grade adenocarcinoma (10 cases), basal cell adenoma (3 cases), basal cell adenocarcinoma (1 case), and epithelial-myoepithelial carcinoma (2 cases), were also examined for comparison. In PA, BMP-2 immunoreactivity was detected in the luminal and non-luminal cells of the tubulo-ductal structures, plasmacytoid cells, and other scattered tumor cells in solid areas. In addition, tumor cells in chondroid areas in most cases (14/15), and stellate cells in myxoid areas in many cases (7/19), were also intensely labeled for BMP-2. Furthermore, BMP-2 was also detected in the non-neoplastic ductal cells in salivary glands, whereas no other salivary gland tumors were positively stained for this protein. Type II collagen was localized in the intercellular matrix of chondroid areas and in a few chondroid differentiating cells in myxoid areas, confirming its cartilage-specificity. A proportional relationship was observed between BMP-2 expression and chondroid formation, although BMP-2 was also stained in occasional PAs without chondroid formation. It is speculated that BMP-2 might be secreted by tumor cells and play a role in chondroid formation in PA by inducing some tumor cells to produce type II collagen and other chondroid matrical substances, like glycosaminoglycans. The expression of BMP-2 is specific to PA and may possibly be used as a useful marker in differentiating PA from other salivary gland tumors.