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Bone Morphogenetic Protein-6 Is a Marker of Serous Acinar Cell Differentiation in Normal and Neoplastic Human Salivary Gland¹

Institute of Dentistry, University of Turku, FIN-20520 Turku, Finland [A. K. H., M. A. L.], Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, FIN-00014 Helsinki, Finland [O. V-P. R.], Haartman Institute, Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland [R. J. V., I. V. L.], Department of Pediatrics, Kuopio University Hospital, FIN-70210 Kuopio, Finland [R. J. V.], and Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee [B. L. M. H.]

Bone morphogenetic protein (BMP-6, also known as vegetal-pale-gene-related and decaplentaplegic-vegetal-related) is a member of the transforming growth factor- superfamily of multifunctional signaling molecules. BMP-6 appears to play various biological roles in developing tissues, including regulation of epithelial differentiation. To study the possible involvement of BMP-6 in normal and neoplastic human salivary glands, we compared its mRNA and protein expression in 4 fetal and 15 adult salivary glands and in 22 benign and 32 malignant salivary gland tumors. In situ hybridization and Northern blot analysis indicated that BMP-6 transcripts are expressed at low levels in acinar cells of adult submandibular glands but not in ductal or stromal cells. BMP-6 was immunolocated specifically in serous acini of parotid and submandibular glands. None was found in primitive fetal acini or any other types of cell in adult salivary glands, including mucous acini and epithelial cells of intercalated, striated, and excretory ducts. All 16 cases of acinic cell carcinoma consistently exhibited cytoplasmic BMP-6 staining in the acinar tumor cells. Other cell types in these tumors, including intercalated duct-like cells, clear, vacuolated cells, and nonspecific glandular cells, exhibited no cytoplasmic BMP-6 staining. Other benign and malignant salivary gland tumors lacked BMP-6 immunoreactivity, except in areas of squamous differentiation. The results indicate that in salivary glands, BMP-6 expression is uniquely associated with acinar cell differentiation and suggest that BMP-6 may play a role in salivary gland function. More importantly, our experience of differential diagnostic problems related to salivary gland tumors suggests that the demonstration of consistent and specific BMP-6 immunoreactivity in acinic cell carcinoma is likely to be of clinical value.

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