Examination of epithelial changes in middle ear cholesteatoma.

Local Infiltration and bony destruction are characteristic features of chol esteatomas. The aim of the study was assessment of cell ploidy, proliferati on rates and expression of cell adhesion molecules to analyze the pathogene tic role of matrix (epithelium) in cholesteatoma. The cellbiologic paramete rs were compared to clinical findings. Patients and Method: Tissue samples from 48 patients with cholesteatomas were analyzed by: routine histology, q uantitative DNA-cytometry with the DNA Indices: 2cDeviation Index (2cDI) an d 5c Exceeding Rate (5c ER), immunohistochemical analysis of proliferation rate (ki67-MIB1 and PCNA), cell adhesion molecules, cell-cell interaction: E-Cadherin, alpha1 beta6-Integrin, Inter-Cellular-Adhesion-Molecule (I-CAM) , cell-matrix interaction: CD44v4/5, CD 44V6, alphav-, beta3-lntegrinchains and vascular-Cell-Adhesion-Molecule (V-CAM). Clinical data included patien t age, history of ear disease, pre-operative audiometry, intra-operative si ze and extension of the cholesteatoma, destruction of ossicles and petrous bone. For comparison healthy squamous epithelium was obtained from the exte rnal ear canal of 10 patients during stapes surgery. Results: Ossicular des tructions were found in 34 cases. Three patients had mesotympanic cholestea tomas, four patients had mesotympanic and epitympanic involvement. In 37 pa tients cholesteatomas extended into the mastoid and in four patients the pe rilabyrinth and the petrous apex were reached. DNA-cytometric examination o f matrix showed normal diploid values and no aneuploid cells (DNA-content > 5c) in all patients. The proliferation rates of the matrix were increased in comparison to normal epithelium. Cell adhesion molecules for intercellul ar bindings were expressed in similar pattern in cholesteatomas and in norm al epithelium. Cell adhesion molecules for cell matrix bindings showed new or increased expression in cholesteatomas. No significant correlation betwe en proliferation and clinical findings could be established. Conclusion: Th e study confirms previous suggestions that the growth of cholesteatomas is not stimulated by the matrix. The increased proliferation of the matrix is a result of the inflammatory process in the cholesteatoma and is correlated to the size of the cholesteatoma. On a cellular or molecular level no corr elation between bone destruction through the cholesteatoma and proliferatio n rate of the cholesteatomas could be established. These findings support s uggestions that the perimatrix of the cholesteatomas is the main pathogenet ic factor.