Characterisation of Acquired Human Cholesteatoma in Ontogenetic Aspect. Summary of the Doctoral Thesis
Authors:   ,   Rīga Stradiņš University, Dambergs Kristaps 
Published: December 2024

Cholesteatoma is a benign, but locally aggressive formation in the middle ear. Human cholesteatoma may be congenital or acquired. Acquired cholesteatoma occurs when skin epithelium migrates into the middle ear where it transforms into cholesteatoma tissue. Cholesteatoma tissue is hyperproliferative and erodes surrounding tissue in the middle ear. The most common patient complaints are impaired hearing and frequent otorrhoea. However, a cholesteatoma can cause complications such as meningitis, brain abscess, facial nerve palsy and sigmoid sinus thrombosis. The morphopatogenesis of cholesteatoma is a complex process characterised by proliferation, the presence of inflammation and remodelling of surrounding tissue. The aim of the study was to determine and describe the relative amount of tissue factors that characterise the morphopatogenetic processes of acquired cholesteatoma and their interaction with each other in the ontogenetic aspect. The study included cholesteatoma tissue from 50 patients. The patients were divided into two groups according to their age, a group of children and a group of adults. Each group consisted of 25 patients. The control group consisted of unaltered skin of seven different deceased people taken from the outer ear meatus. The immunohistochemical method was used to assess the relative amount of matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), tissue inhibitor of matrix metalloproteinase 4 (TIMP-4), proliferation marker Ki-67, nuclear factor kappa beta (NF-κβ), interleukin 1 alpha (IL-1 α), interleukin 10 (IL-10), human beta defensin 2 (HβD-2), human beta defensin 4 (HβD-4), vascular endothelial growth factor (VEGF) and Sonic hedgehog (SHH) gene protein in both cholesteatoma and control tissues. Healthy tissues were characterised by a stable relative balance of remodelling factors (MMP/TIMP) and pro- and anti-inflammatory cytokine complexes (IL-1 α/IL-10), required for normal skin function. In cholesteatoma tissue, an increased expression of Ki-67 was observed, which characterises the hyperproliferation of cells in this formation. Increased expression of NF-κβ also shows the involvement of this factor in cell proliferation and inflammatory processes by enhancing their activity. The overexpression of HβD-2 indicates an intensification of local tissue protection. And the increased number of SHH-positive cells in the perimatrix of the cholesteatoma indicates the intensification of this gene protein in tumour growth. The variable expression of remodelling factors in cholesteatoma tissue indicates an imbalance between remodelling factors. The increase in the number of IL-1α positive structures and the decrease in the number of IL-10 positive cells in cholesteatoma tissue indicate a change in the balance between pro-inflammatory and anti-inflammatory cytokines. Changes in the levels of all these factors are not age-related.
The Doctoral Thesis was developed at Institute of Anatomy and Anthropology of Rīga Stradiņš University, Department of Morphology and Department of Otorhinolaryngology, Latvia. Defence: at the public session of the Promotion Council of Clinical Medicine on December 2024 at 13.30, remotely via online platform Zoom.
3.2 Clinical Medicine; Sub-Sector – Otorhinolaryngology.
Keywords: cholesteatoma; metalloproteinases; Ki-67; transcription factor; defensins; cytokines; vascular endothelial growth factor; sonic hedgehog.