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.