Increased proliferation and migration of epithelium in advancing experimental cholesteatomas

Hypothesis: Hyperproliferative and migratory process of keratinocytes are part of the pathogenesis of cholesteatoma. Background: Cytokeratin (CK) changes were prominent in the most rapidly expanding regions of cholesteatoma formation. Methods: The three types of animal model - canal ligation (CL), retraction pocket (RP), and propylene glycol (PG) - were induced in Mongolian gerbils. The monoclonal antibodies to CK1/10, CK5/6, and CK13/16 were used for immunohistochemistry. The intensity of immunostaining in the pars tensa of the tympanic membrane was measured using the densitometry and compared with respect to the stage of cholesteatoma and the type of animal model. Results: With cholesteatoma formation, CK expressions were significantly increased at the peripheral part of the pars tensa, the expanding part of cholesteatoma. Among the CKs tested, the prominent changes were observed in expression of CK13/16, a marker for hyperproliferation. Among the animal models, CK changes of CK5/6 and CK1/10 were most prominent in the CL type, whereas those of CK13/16 were more persistent in the RP type. Conclusion: These results suggested that complex alterations of epidermal keratinocytes occur during cholesteatoma formation and that hyperproliferative and migratory processes play important roles in the pathogenesis of cholesteatoma.