The Study of the Pathogenesis of Middle Ear Cholesteatoma with Immunohistochemical Staining of Matrix Metalloproteinases, Extracellular Matrix Proteins and T Lymphocyte Distribution / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: The exact pathogenesis of middle ear cholesteatoma is still unknown to some extent. Recently, however, advances of immunology have opened a new chapter in investigating the etiology and pathogenesis of cholesteatoma through immunohistochemical techniques. Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and the accelerated breakdown associated with tumor development. The aim of this study was to investigate the immunohistochemical expression of MMP-2, MMP-3, and MMP-9 in correlation with the expression of basement membrane antigen (laminin), fibronectin and T lymphocyte in middle ear cholesteatoma to compare them with those in external auditory canal skin as a control group. Material and Methods: The biopsy specimens of cholesteatomatous tissue and external auditory canal skin were obtained during undergoing the middle ear surgery. Immunohistochemical staining was carried out using monoclonal mouse antibodies against MMP-2, MMP-3, MMP-9, laminin, fibronectin and pan T lymphocyte (UCHL1) were used. RESULTS: The results are as follows In cholesteatomatous tissue, a number of T lymphocytes were expressed and a large number of MMPs were expressed in the basal cell layer and in the stroma of cholesteatoma. Both MMP-2 and MMP-3 showed positive signals in the basal and parabasal cell layer. A strong expression of MMP-9 was shown in granuloma area. Expression of MMP-3 had a significant correlation with a distribution of T lymphocyte (r=-0.522, p<0.05). Expression of MMP-2 had a significant correlation with a distribution of laminin (r=0.662, p <0.05). CONCLUSION: These results indicate that spatial distribution of matrix metalloproteinases in the extracellular matrix show a specific relation to extracellular matrix molecules such as laminin, fibronectin and T-lymphocyte in middle ear cholesteatoma especially inflammatory and immune state.