Remodeling Factors, Transcription Factors and Angiogenetic Factors in Cholesteatoma in Ontogenetic Aspect.

Introduction: The main goal of our study was to describe the transcription factor (NF-κß), angiogenetic factor (VEGF), and remodeling markers (MMP-9 and TIMP-4) of the cholesteatoma tissue compared to control skin tissue. There are still uncertainties how transcription, angiogenetic and remodeling factors affect the cholesteatoma course. Materials and Methods: Eight cholesteatoma tissue specimens were retrieved from children, seven - from adults, seven skin controls - from cadavers. Obtained material immunohistochemically were stained for NF-κß, MMP-9, TIMP-4, VEGF. Non-parametric statistic methods were used. Results: A statistically significant higher numbers of NF-κß and TIMP-4 immunoreactive cells in the cholesteatoma compared to control group. A very strong positive correlation between MMP-9 and TIMP-4 was seen in the patient group. A strong positive correlation - between MMP-9 in matrix and MMP-9, VEGF in perimatrix, between TIMP-4 in matrix and TIMP-4 in perimatrix, NF-κß in the matrix and VEGF; between TIMP-4 in perimatrix and NF-κß in the matrix. Conclusions: Correlation between MMP-9 and TIMP-4 suggests that TIMP-4 in cholesteatoma tissue intercorrelates to MMP-9. TIMP-4 likely regulates the development of cholesteatoma. Disbalance between MMPs and TIMPs affects NF-κß and causes uncontrolled cell proliferation and immune response in this tumor. There is a lack of VEGF strong expression in cholesteatoma perimatrix.