KERATINOCYTE DIFFERENTIATION IN ACQUIRED CHOLESTEATOMA AND PERFORATEDTYMPANIC MEMBRANES

Objective: To evaluate the type of differentiation of keratinocytes of acquired cholesteatoma and its significance for cholesteatoma invasiv eness. Design: Forty acquired cholesteatomas and 10 tympanic membranes with persisting perforations were snap frozen and processed for immun ohistochemical studies. Cytokeratin antibodies that represented all su bgroups and antibodies that were directed against collagen components of the basal lamina were applied. Expression of these constituents was scored by using light microscopy. Results: The phenotype of the matri x was generally characterized by an extension of expression of basal c ell cytokeratin 14 and hyperproliferation-associated cytokeratins 6, 1 6, and 17 into the suprabasal cell layers, while the expression of ker atinization marker cytokeratin 10 was down-regulated. These features v aried greatly at different sites of the matrix and were most marked at the advancing front of the cholesteatoma. A comparable expression pat tern, but less pronounced, was observed at the epidermal front of the mucocutaneous junction of the tympanic membrane perforations. This phe nomenon was invariably associated with a mononuclear cell infiltrate i n the dermis at both junctions. The basal lamina was always intact. Co nclusions: Acquired cholesteatomas show hyperproliferative features. T here is a striking similarity between the pronounced expression of thi s phenotype and the associated inflammation at the mucocutaneous junct ions of cholesteatomas and tympanic membrane perforations and those th at are observed after epidermal injury. This indicates that epidermis and middle ear epithelium do not form stable junctions and the front c an be considered to be a persisting epidermal defect. This involves th e permanent presence of ''activated keratinocytes'' in the junction ar ea that will lead to proliferation and migration, when additional trig gers are present.