keratan-sulfate and Adenoma--Pleomorphic

Pleomorphic adenomas are the most common salivary gland tumour. Although this tumour is considered to be of epithelial origin, it contains 'mesenchyme'-like elements histologically. Lumican is a keratan sulphate proteoglycan that belongs to the small leucine-rich repeat (LRR) proteoglycans and has been reported to be associated with cartilage formation. These findings suggest that lumican expression may be related to the chondroid component in pleomorphic adenomas. To investigate this hypothesis, the present study investigated the expression and localization of lumican in 20 normal human salivary glands and 35 pleomorphic adenomas. Firstly, immunohistochemistry for lumican was performed with pepsin pretreatment. In normal salivary glands, lumican was deposited in the periductal regions. In pleomorphic adenomas, it was predominantly deposited in the hyaline (100%) and fibrous areas (89.4%). In 16 tumours (66.7%), lumican was also deposited in the chondroid areas. Without pepsin pretreatment, lumican was identified in myoepithelial cells in myxoid areas, lacuna cells in chondroid areas, and in the cytoplasm of inner ductal cells. In situ hybridization revealed lumican mRNA expression mainly in the inner cells, the neoplastic myoepithelial cells, and the lacuna cells. These results suggest that lumican is associated with the formation of 'mesenchyme'-like structures in pleomorphic adenomas. In conclusion, normal salivary glands express lumican, which appears to be related to stromal maintenance, and pleomorphic adenomas express lumican mRNA and protein, which may play important roles in the formation of 'mesenchyme'-like areas in this type of tumour.

Topics: Adenoma, Pleomorphic; Chondroitin Sulfate Proteoglycans; Gene Expression; Humans; In Situ Hybridization; Keratan Sulfate; Lumican; Mesoderm; Neoplasm Proteins; RNA, Messenger; Salivary Gland Neoplasms; Salivary Glands

The tumor matrix of salivary pleomorphic adenoma (PA) is characteristically rich in glycosaminoglycans (GAGs), which contribute to its complex histoarchitecture. This study evaluated the microscopic localization of various GAGs in 17 PAs, using a panel of anti-GAG monoclonal antibodies and biotinylated hyaluronic acid (HA)-binding protein. Both epithelial and mesenchymal-like tissues were confirmed to contain GAGs. Luminal epithelial cells mostly lacked GAGs, whereas GAGs were seen both in the cytoplasm and cell membrane of non-luminal epithelial cells. In addition, small intercellular accumulations of GAGs were often present in solid epithelial areas, implying the epithelial origin of GAGs. GAGs did not appear to be a main component of the hyaline matrix. The myxoid region was consistently stained for both chondroitin 6-sulfate (CS-6) and HA but variably for chondroitin 4-sulfate (CS-4), dermatan sulfate (DS) and keratan sulfate (KS); heparan sulfate (HS) was not detected. The chondroid region showed increased staining for CS-6 but reduced staining for HA when compared with the myxoid region. In addition, CS-4, DS and KS were seen both in chondroid cells and the territorial matrix, whereas HS was present only in the cells. It is suggested that GAGs in PA are mainly produced by non-luminal cells and influence the proliferation, differentiation, secretory activity and shape of tumor cells, thus contributing to the morphological diversity of this tumor.

Topics: Adenoma, Pleomorphic; Antibodies, Monoclonal; Cell Differentiation; Cell Division; Cell Membrane; Cell Size; Chondroitin Sulfates; Cytoplasm; Dermatan Sulfate; Epithelial Cells; Epithelium; Extracellular Matrix; Glycosaminoglycans; Heparitin Sulfate; Histocytochemistry; Humans; Hyaluronic Acid; Immunohistochemistry; Keratan Sulfate; Mesoderm; Salivary Gland Neoplasms