“…Hyperproliferation markers include Cytokeratin 16 (CK16), antigen Ki-67 and Proliferating Cell Nuclear Antigen (PCNA), which are overexpressed in the annulus tympanicus, adjacent meatus and tympanic regions [71]. The inflammation-driven epithelial proliferation is associated with an increased expression of lytic enzymes and cytokines including arachidonic acid, Intercellular Adhesion Molecule (ICAM), Receptor Activator Of Nuclear Factor Kappa-B Ligand (RANKL), Interleukin-1,-2 and -6 (IL-1, IL-2, IL-6), Matrix Metalloproteinase-2 and -9 (MMP-2, MMP-9) as well as Tumor Necrosis Factor-alpha (TNF-alpha), which are partly induced by bacterial antigens [61,68,72] including endotoxins like lipopolysaccharides [67]. Increased proliferative activity of epithelial cells is associated with increased nuclear content in the basal cells of colesteatoma as the morpholocial correlate of basal hyperplasia, being particularly pronounced in areas of inflammatory infiltration [73].…”