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-κβ), angiogenetic factor (VEGF), and remodeling markers (MMP-۹ and TIMP-۴) 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-κβ, MMP-۹, TIMP-۴, VEGF. Non-para­metric statistic methods were used. Results:A statistically significant higher numbers of NF-κβ and TIMP-۴ immunoreactive cells in the cholesteatoma compared to control group. A very strong positive correlation between MMP-۹ and TIMP-۴ was seen in the patient group. A strong positive correlation - between MMP-۹ in matrix and MMP-۹, VEGF in perimatrix, between TIMP-۴ in matrix and TIMP-۴ in perimatrix, NF-κβ in the matrix and VEGF; between TIMP-۴ in perimatrix and NF-κβ in the matrix. Conclusions:Correlation between MMP-۹ and TIMP-۴ suggests that TIMP-۴ in cholesteatoma tissue intercorrelates to MMP-۹. TIMP-۴ likely regulates the development of cholesteatoma. Disbalance between MMPs and TIMPs affects NF-κβ and causes uncontrolled cell proliferation and immune response in this tumor. There is a lack of VEGF strong expression in cholesteatoma perimatrix. 

Keywords:

Cholesteatoma , Transcription factor , Metalloproteases , Vascular Endothelial Growth Factor