The aim of this study was to describe the appearance and distribution of tissue remodeling markers (MMP-2, MMP-9, TIMP-2, TIMP-4), Sonic hedgehog gene protein (Shh), pro- and anti-inflammatory cytokines (IL-1, IL-10), transcription factor (NF-κβ), proliferation marker (Ki-67), angiogenetic factor (VEGF), tissue defensins (HβD-2, HβD-4) of the pediatric cholesteatoma. Sixteen cholesteatoma samples were obtained from children, eleven skin controls from cadavers. Tissues were stained for MMP-2, MMP-9, TIMP-2, TIMP-4, Shh, IL-1, IL-10, NF-κβ, Ki-67, VEGF, HβD-2, HβD-4. Non-parametric statistic, Mann-Whitney, and Spearman's coefficient was used. A statistically significant difference was seen between Shh and HβD-2 in perimatrix and control connective tissue, between NF-κβ in cholesteatoma and control skin, and between HβD-4 in matrix and skin epithelium. Complex intercorrelations between MMPs, NF-κβ and VEGF cause the intensification of angiogenesis in cholesteatoma. The persistent increase in Shh gene protein expression in cholesteatoma perimatrix suggests the stimulation of the cholesteatoma growth in children. Similar expression of IL-1 and IL-10 and their intercorrelation, proves there is a balance between pro- and anti-inflammatory cytokines. NF-κβ, and not Ki-67, seems to be the main inducer of cellular proliferation. The main antimicrobial protection is provided by HβD-2.
Keywords: Ki-67; children; cholesteatoma; cytokines; defensins; metalloproteases; sonic hedgehog; transcription factors; vascular endothelial growth factor.