Alteration of epidermal differentiation in middle ear cholesteatoma

This immunohistologic study was undertaken to compare the localization of markers of epidermal differentiation in cholesteatoma and normal external ear canal skin. Both basal cells and suprabasal cell layers of cholesteatoma exhibit an abnormal distribution of differentiation markers (involucrin, filaggrin, glycoproteins detected by monoclonal antibodies J143 [alpha3 integrin chain] and T16 [Trop-2]). The immunostaining intensity of filaggrin and involucrin was higher in cholesteatoma than in external ear canal skin. In cholesteatoma, involucrin was localized in the cytoplasm of the suprabasal cells, and particularly in spinous cells, it appeared earlier than in ear canal skin. Filaggrin was noted in the cytoplasm of the granular and cornified cells in both tissues. The J143 reactive integrin, very late antigen 3 (VLA-3), which in normal epidermis is confined to the basal cells, was also seen in spinous and granular cell layers of cholesteatoma. Furthermore, the immunostaining for VLA-3 in the basal cell layer of cholesteatoma was stronger than in normal epidermis. In contrast to this, expression of Trop-2, which is preferentially found in the suprabasal cell layers, particularly in granular cells of normal epidermis, was clearly reduced in cholesteatoma. These results demonstrate complex alterations in the differentiation of the keratinocytes in cholesteatoma.