[Epithelium-stroma interaction in cholesteatoma of the middle ear].

Background: Local Infiltration and bony destruction are characteristic features of cholesteatomas. The aim of the study was assessment of cell ploidy, proliferation rates and expression of cell adhesion molecules to analyze the pathogenetic role of matrix (epithelium) in cholesteatoma. The cellbiologic parameters were compared to clinical findings.

Patients And Method: Tissue samples from 48 patients with cholesteatomas were analyzed by: routine histology, quantitative DNA-cytometry with the DNA indices: 2cDeviation Index (2cDI) and 5c Exceeding Rate (5c ER), immunhistochemical analysis of proliferation rate (ki67-MIB1 and PCNA), cell adhesion molecules, cell-cell interaction: E-Cadherin, alpha 1 beta 6-Integrin, Inter-Cellular-Adhesion-Molecule (I-CAM), cell-matrix interaction: CD44v4/5, CD 44v6, alpha v-, beta 3-Integrinchains and vascular-Cell-Adhesion-Molecule (V-CAM). Clinical data included patient age, history of ear disease, pre-operative audiometry, intra-operative size and extension of the cholesteatoma, destruction of ossicles and petrous bone. For comparison healthy squamous epithelium was obtained from the external ear canal of 10 patients during stapes surgery.

Results: Ossicular destructions were found in 34 cases. Three patients had mesotympanic cholesteatomas, four patients had mesotympanic and epitympanic involvement. In 37 patients cholesteatomas extended into the mastoid and in four patients the perilabyrinth and the petrous apex were reached. DNA-cytometric examination of 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 intercellular bindings were expressed in similar pattern in cholesteatomas and in normal epithelium. Cell adhesion molecules for cell matrix bindings showed new or increased expression in cholesteatomas. No significant correlation between proliferation and clinical findings could be established.

Conclusion: The 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 correlation between bone destruction through the cholesteatoma and proliferation rate of the cholesteatomas could be established. These findings support suggestions that the perimatrix of the cholesteatomas is the main pathogenetic factor.