Morphopathogenesis of adult aquired cholesteatoma

Background and Objectives. The aim of this study was to compare the distribution of proliferation
markers (Ki-67, NF-κβ), tissue-remodeling factors (MMP-2, MMP-9, TIMP-2, TIMP-4), vascular
endothelial growth factor (VEGF), interleukins (IL-1 and IL-10), human beta defensins (HβD-2 and HβD4) and Sonic hedgehog gene protein in cholesteatoma and control skin. Methods. Nineteen patient
cholesteatoma tissues and seven control skin materials from cadavers were included in the study and
stained immunohistochemically. Results. Statistically discernible differences were found between the
following: the Ki-67 in the matrix and the Ki-67 in the skin epithelium (p = 0.000); the Ki-67 in the
perimatrix and the Ki-67 in the connective tissue (p = 0.010); the NF-κβ in the cholesteatoma matrix and
the NF-κβ in the epithelium (p = 0.001); the MMP-9 in the matrix and the MMP-9 in the epithelium (p =
0.008); the HβD-2 in the perimatrix and the HβD-2 in the connective tissue (p = 0.004); and the Shh in the
cholesteatoma’s perimatrix and the Shh in the skin’s connective tissue (p = 0.000). Conclusion. The
elevation of Ki-67 and NF-κβ suggests the induction of cellular proliferation in the cholesteatoma.
Intercorrelations between VEGF, NF-κβ and TIMP-2 induce neo-angiogenesis in adult cholesteatoma.
The similarity in the expression of IL-1 and IL-10 suggests the dysregulation of the local immune status
in cholesteatoma. The overexpression of the Sonic hedgehog gene protein in the cholesteatoma proves
the selective local stimulation of perimatrix development.