Transcription and remodelling factors in the development of cholesteatoma from an ontogenetic aspect compared to deep external ear skin controls

There are still uncertainties how transcription and remodelling factor contribute to the pathogenesis of cholesteatoma. The main goal of our work was to describe the appearance and distribution of remodelling markers (MMP-9 and TIMP-4), and transcription factor (NF-κβ) in cholesteatoma compared to control skin tissue. Eight cholesteatoma tissue samples were obtained from eight children, five boys and three girls (age 9–17 years, mean age 14.87 years). Seven cholesteatoma specimens were obtained from seven adults, two male and five female patients (age 23–75 years, mean age 42.71 years). Seven deep external meatal skin controls were obtained from cadavers from a collection in the Institute of Anatomy and Anthropology. Tissues were immunohistochemically stained for NF-κβ, MMP-9, TIMP-4. The slides were analysed by light microscopy using a semi-quantitative method. Non-parametric statistical analysis - Mann-Whitney and Spearman’s coefficient - was used to detect statistical differences and correlations. Statistically significant difference was observed between the number of NF-κβ positive cells in matrix and perimatrix compared to control group skin epithelium and connective tissue. Moreover, there was a statistically significant difference between the number of TIPM-4 positive cells in the perimatrix and the TIMP-4 positive cells in control connective tissue. A very strong positive correlation in the patient group was detected between MMP-9 and TIMP-4. A strong positive correlation was seen between MMP-9 positive cells in matrix and MMP-9 in perimatrix, between TIMP-4 in matrix and TIMP-4 in perimatrix and between TIMP-4 in perimatrix and NF-κβ in the matrix. Correlation between MMP-9 and TIMP-4 suggests that TIMP-4 intercorrelates to MMP-9 in cholesteatoma tissue. Disbalanced ratio between MMP-9 and TIMP-4 affects NF-κβ and causes uncontrolled cell proliferation and immune response in cholesteatoma. A statistically significant difference between TIMP-4 in perimatrix and skin connective tissue indicates that TIMP-4 most likely regulates the development of cholesteatoma.