Expression of cytokeratins 13 and 16 in middle ear cholesteatoma

The accumulation of keratinizing epithelium in the middle ear cavity is a crucial factor in the pathogenesis of cholesteatoma. We hypothesize that keratinocytes from the skin of the ear canal migrate and hyperproliferate in response to inflammation in the middle ear cavity to cause accumulation of keratin debris. In the present study, we investigated the expression of specific cytokeratins (CKs) in the cholesteatoma matrix to determine whether cholesteatoma is a hyperproliferative disease. Cytokeratin expression was examined in cholesteatoma, meatal skin, and tympanic membrane with two monoclonal antibodies, one for both cytokeratins 13 and 16 (antibody K8.12), and another for cytokeratin 13 only (antibody KS-1A3). CK 13 (MW 51 KD) is a marker of differentiation and CK 16 (MW 48 KD) is a marker of hyperproliferation of keratinocytes. The use of immunoblot probes showed that CKs 13 and 16 were present in cholesteatoma. Immunofluorescent staining showed the presence of CK 16 in the suprabasal layer of cholesteatoma, which was located near the external ear canal. CK 13 was localized in the suprabasal layer of meatal skin and tympanic membrane. CK 13 was localized in the basal layer of the cholesteatoma, distal to the external ear canal, but not in the meatal skin and tympanic membrane. Taken together, the present data suggest that cholesteatoma is a hyperproliferative disease and that cholesteatoma expresses CK 16 near the external ear canal and transforms to express CK 13 during growth distally.