Cytokines and adhesion molecules in middle ear cholesteatoma. A role in epithelial growth?

The immune response is thought to play a role in dysregulating epithelial growth in cholesteatoma of the middle ear. Through immunohistochemistry (using 18 monoclonal antibodies) on 10 specimens from human middle ear cholesteatomas, T-helper cells mixed with plasma cells, macrophages and scattered T-suppressor and B cells, have been detected in the perimatrix. Mast cells have also been identified in the perimatrix, usually close to the epithelium. Elements positive for D-related human leukocyte antigens (HLA-DR) were more than half of the immune cells. The endothelium of the perimatrix showed a sharp reactivity to the intercellular adhesion molecule-1 (ICAM1) and to the endothelial derived leukocyte adhesion molecule-1 (ELAM1), which play a role in recluting inflammatory cells and modulating the immune response. The expression of ICAM1 in the basal layer of the matrix indicates the homing of inflammatory reactions at the epithelial-stromal junction of the cholesteatoma. An intense expression of interferon-gamma receptor (IFN gamma R) was found in the basal layers of the cholesteatoma matrix, and overexpression of the epithelial growth factor receptor (EGFR) was found in all layers of the matrix. These data support the hypothesis that the epithelial cells in middle ear cholesteatoma are in an activated state and that their hyperproliferation is mediated through cytokines and adhesion molecules.