Expression and localization of cartilage-specific matrix protein chondromodulin-I mRNA in salivary pleomorphic adenomas

Abstract

Pleomorphic adenoma is the most common epithelial tumor in the salivary glands. This tumor frequently exhibits "mesenchyme"-like components, including myxoid or chondroid areas. Recently, using immunohistochemical techniques, we reported that cartilage-specific matrix protein, chondromodulin-I (ChM-I), was deposited on the inter-territorial matrix of the chondroid area in salivary pleomorphic adenomas and that ChM-I, which is also a strong angio-inhibitory factor, plays an important role in the avascular nature of the chondroid area and the chondroid formation in this type of tumor. To elucidate which cells express ChM-I mRNA in pleomorphic adenomas, we examined the expression and localization of ChM-I mRNA in this type of tumor using an in situ hybridization technique. Immunoreactivity for ChM-I was observed in the inter-territorial matrix of the chondroid area, especially around the lacunae, and in the cytoplasm of neoplastic myoepithelial cells of the myxoid element of pleomorphic adenomas. On in situ hybridization analysis, strong signals for ChM-I mRNA were detected in the cytoplasm of the lacuna cells of the chondroid element, and moderate to marked signals were observed in the cytoplasm of the neoplastic myoepithelial cells of the myxoid element. Signals for ChM-I mRNA were also seen in the cytoplasm of the spindle-shaped neoplastic myoepithelial cells in the transitional areas between the myxoid and chondroid elements of this tumor. Signals for ChM-I mRNA were not seen in the inner ductal cells or the fibrous element. These findings indicate that lacuna cells and neoplastic myoepithelial cells express ChM-I mRNA and that mature ChM-I, which lacuna cells and neoplastic myoepithelial cells translate, is deposited in the chondroid matrix of pleomorphic adenomas. In conclusion, lacuna cells and neoplastic myoepithelial cells express ChM-I mRNA ectopically in pleomorphic adenoma, and this plays an important role in chondroid formation and hypovascularity in this type of tumor.

Chondromodulin-I and Tenomodulin: The Negative Control of Angiogenesis in Connective Tissue

“…Pleomorphic adenoma of the salivary glands is characterized by the mixed appearance of epithelial and mesenchymal-like elements, and the expression of ChM-I in this disease is associated with the formation of chondroid elements and inversely correlates with the presence of a CD34 endothelial marker [79,80]. This suggests that ChM-I is involved in both hypovascularity and in chondroid differentiation in this type of tumor.…”

Minute pleomorphic adenoma of the submandibular gland in patients with oral malignancy: a report of two cases with histological and immunohistochemical examination

“…1 This paper adds to several others published in recent years on distinguishing primary serosal neoplasms from metastases originating from lung and extrapulmonary carcinoma. [2][3][4][5][6][7] As pointed out by these studies, positive and negative mesothelioma markers do not have universal diagnostic usefulness, since their specificity and sensitivity vary according to individual conditions. The use of a small panel of antibodies with a high combined sensitivity and specificity is therefore recommended.…”

“…PA is a hypovascular tumour due to the low density of CD34+ endothelial cells 3 . We have previously reported that cartilage‐specific matrix protein, chondromodulin‐I (ChM‐I) protein and mRNA are expressed in PA 3,4 . ChM‐I serves as a barrier against angiogenic factors, providing a possible explanation for PA being a hypovascular tumour.…”

“…We have reported that bone morphogenetic proteins are associated with chondroid formation in PA. 1,2 PA is a hypovascular tumour due to the low density of CD34+ endothelial cells. 3 We have previously reported that cartilage-specific matrix protein, chondromodulin-I (ChM-I) protein and mRNA are expressed in PA. 3,4 ChM-I serves as a barrier against angiogenic factors, providing a possible explanation for PA being a hypovascular tumour. A major cartilage proteoglycan, aggrecan, has also been shown to be deposited in the chondroid elements of PA. 3 Neoplastic myoepithelial cells in PA may play an important role in chondroid formation in PA. 5,6 However, the histogenesis of PA is unknown.…”