Expression of disintegrin and metalloproteinase family proteins 10, 12 and 17 in cholesteatoma S ERBEK 1 , H ERINANC 2 , E HIZAL 1 , L N OZLUOGLU 1 Departments of 1 Otolaryngology Head and Neck Surgery, and 2 Pathology, Faculty of Medicine, Baskent University, Ankara, Turkey Abstract Objective: Proteases of the disintegrin and metalloproteinase family (also known as ADAM proteins) are involved in various physiological and pathological processes. This study assessed the expression of disintegrin and metalloproteinase family proteins 10, 12 and 17 in cholesteatoma. Materials and methods: The study evaluated cholesteatoma specimens from 19 patients, and external ear canal skin samples from 7 of the same patients (as controls), for the expression of disintegrin and metalloproteinase family proteins 10, 12 and 17, using immunohistochemical methods. Results and analysis: The study observed over-expression of proteins 10 and 17 in blood vessels, and over- expression of proteins 12 and 17 in cholesteatoma stroma. Immunostaining scores for proteins 10, 12 and 17 in epithelial and inflammatory cells from cholesteatoma specimens versus control specimens showed no statistically significant differences. Conclusion: Over-expression of disintegrin and metalloproteinase family proteins 10, 12 and 17 in cholesteatoma may be related to cholesteatoma pathogenesis. These proteins deserve further study as they may represent potential targets for cholesteatoma treatment. Key words: Cholesteatoma; ADAM proteins; ADAM-10 protein, human; ADAM12 protein, human; ADAM17 protein, human Introduction The pathophysiology of acquired cholesteatoma con- tinues to be controversial. Growing evidence leads us to consider the genesis, expansion and progression of cholesteatoma as a complex interaction between the anatomical, inflammatory and regulatory factors involved in cellular proliferation and differentiation. Over the past two centuries, our understanding of cho- lesteatoma has been improved by the theories of inva- gination, basal cell hyperplasia or papillary ingrowth, metaplasia, and epithelial invasion. However, the exact mechanisms responsible for the invasion, recidi- vism and destruction seen in this disease remain unclear. 1 The role of enzymatic and cytokine-mediated inflammation in the pathogenesis of cholesteatoma has been studied in recent decades. Certain members of the metalloproteinase superfamily (matrix metallo- proteinases 2 and 9) have been shown to play some role in the process. 2– 4 The disintegrin and metalloproteinase family of pro- teins (also known as ADAM proteins) are members of the metalloproteinase superfamily. 5,6 They are unique, multidomain transmembrane and secreted proteins which are capable of mediating cell adhesion, migration, development and signalling. Proteases of the disintegrin and metalloproteinase family are involved in a variety of physiological processes, and also in the pathogenesis of various inflammatory and hyperproliferative diseases, including cancer. 6,7 One of their best-established functions is the release of bio- logically important ligands such as tumour necrosis factor α (TNF-α), epidermal growth factor, transform- ing growth factor α and amphiregulin. 6 Because these ligands have been implicated in the pathogenesis of cholesteatoma, it might be expected that the specific disintegrin and metalloproteinase family proteins involved in their release would also be involved in the formation of cholesteatoma. In this study we aimed to elucidate the expression of disintegrin and metalloproteinase family proteins 10, 12 and 17 in cholesteatoma tissues, and to investigate the possible role of these proteins in the pathogenesis of cholesteatoma. Presented at the 1st Turkish National Congress of Otology and Neurotology, 12–16 May 2010, Gazimagosa, Cyprus Accepted for publication 25 April 2012 First published online 15 January 2013 The Journal of Laryngology & Otology (2013), 127, 153–158. MAIN ARTICLE © JLO (1984) Limited, 2013 doi:10.1017/S0022215112003106