Proliferation Markers, Remodeling Factors, Cytokines, Antimicrobial Peptides and Gene Proteins in Cholesteatoma

Introduction: The complex appearance of proliferation markers, cytokines, remodelling factors, antimicrobial peptides and genes still have not been studied together despite their possible crucial role in the development of cholesteatoma. Therefore, the
aim of this study was complex research of appearance and distribution of proliferation,remodeling markers, pro- and anti-inflammatory cytokines, local tissue defensins and genes of the cholesteatoma tissue.
Materials and Methods: Four cholesteatoma tissue samples were obtained from children, 5 cholesteatoma specimens were obtained from adults, and 7 deep external meatal skin controls were obtained from cadavers. Tissues were stained for Ki-67,
MMP-2, TIMP-2, IL-1, IL-10, HβD-2, HβD-4 and Shh immunohistochemically. Non-parametric statistic, Mann-Whitney and Spearman’s coefficient were used.
Results: A statistically significant difference was seen between the numbers of Ki67, TIMP-2 positive cells in matrix and control group epithelium and between numbers of HβD-2, HβD-4 Shh positive cells in perimatrix in comparison to control group connective tissue. A very strong positive correlation was detected in control tissue epithelium between Ki-67 and TIMP-2, IL-10, Shh; between MMP-2 and TIMP-2, IL-1; between IL-10 and TIMP-2, Shh. In the connective tissue, a very strong correlation was detected between Ki-67 and Shh. A strong correlation was detected in epithelium between Ki-67 and MMP-2, and between MMP-2 and IL-10.
Conclusion: Cholesteatoma tissue with the low appearance of Ki-67 proves the indistinct proliferation activity in the already developed tumour, but Ki-67 correlations with HβD-2 and HβD-4 in cholesteatoma indicate the direct link between the proliferation and expression of antimicrobial peptides. HβD-2 seems to be the most important factor for antimicrobial defence, but the correlations between HβD-2 and HβD-4 suggest their common action against chronic middle ear infection in case of choleasteatoma.
Higher levels of MMP-2 positive cells in cholesteatoma and lower levels of TIMP-2 positive cells suggest the prevalence of enzymatic processes over their suppression, possibly being characteristic for cholesteatoma of different age patients. Shh gene might play a crucial role in the development of cholesteatoma.