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Despite the identical codon 105 mutation and codon 129 polymorphism of the PrP gene, remarkable clinical and neuropathologic differences, and PrP heterogeneity were present between the affected siblings. The phenotypic variability might be related to PrP heterogeneity.

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Salivary pleomorphic adenomas are often associated with chondroid tissue formation. We investigated the relationship between chondroid tissue formation and the expression of bone morphogenetic proteins (BMPs), which are strong inducers of ectopic bone and cartilage formation. Fifteen pleomorphic adenomas and seven normal salivary glands were examined genetically and immunohistochemically. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that BMP-1, BMP-2, BMP-3, BMP-4, and BMP-7 mRNAs were overexpressed in 10 (66.7%), 9 (60.0%), 1 (6.7%), 8 (53.3%), and 12 (80.0%), respectively, of the 15 pleomorphic adenomas. Overexpression of BMP-2 mRNA was observed in pleomorphic adenomas. Marked chondroid formation or expression of type II collagen was frequently observed in pleomorphic adenomas that overexpressed BMP-2 mRNA. Immunohistochemically, BMP-2 was detected in modified myoepithelial cells aroud chondroid tissue and basement membranes. These results suggest that BMPs, and expecially BMP-2, have a role in chondroid formation in pleomorphic adenomas.

Chondromodulin-I (ChM-I) is a novel cartilage-specific matrix protein. In the growth plates of the long bones, ChM-I was shown to be expressed in mature to upper hypertrophic chondrocytes, and to be deposited in the cartilage matrix. As ChM-I strongly inhibits angiogenesis, cartilage is avascular. Also, ChM-I has bifunctional activity against chondrocyte proliferation. On the other hand, pleomorphic adenomas of the salivary glands frequently have chondroid elements. To elucidate the relationship between chondroid formation and hypovascularity in salivary pleomorphic adenomas, we immunohistochemically examined the expression and localization of ChM-I in 35 cases of this tumor. ChM-I was immunolocalized to the lacunae in the chondroid elements of pleomorphic adenomas (100%). Type II collagen and aggrecan were immunolocalized throughout the matrix around lacuna cells of the chondroid element (100%, 91.7%), and ChM-I was infrequently immunolocalized to the spindle-shaped myoepithelial cells in the myxoid element (37.5%). Fibroblast growth factor-2 was strongly immunolocalized to the lacuna cells in the chondroid element (100%), among the neoplastic myoepithelial cells in the myxoid elements (96.9%), and on the basement membranes around the solid nests of neoplastic myoepithelial cells (71.4%). Although CD34 is a marker of endothelial cells, CD34 was expressed in the endothelial cells in only a few areas around the epithelial elements and in the fibrous element of pleomorphic adenomas. No signals for CD34 were observed in chondroid elements in pleomorphic adenomas (P < 0.001), but a few signals were seen in the myxoid elements (P < 0.05). These findings suggested that lacuna cells and neoplastic myoepithelial cells expressed ChM-I, and that this molecule may play an important role in hypovascularity and chondroid differentiation in pleomorphic adenoma. In conclusion, pleomorphic adenoma expressed ChM-I, which is involved in hypovascularity and chondroid formation in this type of tumor.