Abstract
Cholesteatoma is an epidermal cyst with still unknown pathomechanism. The aim of the current study was to investigate molecular differences in the background of the hyperproliferative property and aggressive behavior typical of the cholesteatoma epithelium. The expression of three cytokeratin genes (KRT1, KRT10 and KRT19), the matrix metalloproteinase 9 gene (MMP9) and the tumor suppressor TP53 gene was measured by qRT-PCR in surgical samples of pediatric and adult cholesteatoma cases and their expression level was compared to that of normal skin samples from the retroauricular region of control individuals. Cholesteatoma samples were stratified according to the age of onset and recurrence for more detailed analysis. Our results showed identical expression pattern for KRT1 and KRT10, their expression was higher in pediatric cases than in adults, especially in pediatric recurrent samples. The expression level of KRT19 was inversely proportional to that of KRT1/KRT10, it was lower in the more invasive recurrent cases both in our pediatric and adult groups. As it was expected from the bone destructive behavior of cholesteatoma, a significantly elevated expression of MMP9 was measured in cholesteatoma samples, the highest level was found in adult recurrent cases. Low expression levels characterize the TP53 gene without significant differences in our samples. These findings demonstrate that cytokeratin expression distinguishes between pediatric/adult, nonrecurrent/recurrent cases, suggesting that distinct differentiation state and cell division potential characterize these cholesteatoma cases. KRT19 with a tumor suppressor potential might restrict the recurrence of cholesteatoma. The differences observed in gene expression profiles between cholesteatoma and control samples support the notion that cholesteatoma is a cystic lesion with tumor-like behavior because it is characterized by invasive, destructive growth and high tendency for recurrence.
Highlights
Aural cholesteatoma is a consequence of chronic middle ear inflammation
The purpose of our study was to investigate the mRNA expression patterns of five selected genes—KRT10 genes located on different chromosomes (KRT1), KRT10, KRT19, matrix metalloproteinase 9 gene (MMP9), and TP53—which might have an influence on the pathogenesis of cholesteatoma, and to identify differences in the multiple gene expression
Patients were divided into two groups according to their age: a pediatric and an adult group both groups were further classified based on the clinical data into primary acquired and recurrent groups
Summary
Aural cholesteatoma is a consequence of chronic middle ear inflammation. Cholesteatoma— previously called as pearl tumor due to its characteristic pocket-like appearance—itself is a keratinous cystic lesion localized in an ectopic position in the middle ear. The epithelial pocket of cholesteatoma is an epidermal cyst enclosed by multilayered keratinized epithelium. Since keratin produced by the keratinized epithelium accumulates inside the pocket which cannot be emptied, the size of the pocket is continuously growing. The locally invasive nature of cholesteatoma—its proliferation and growth—affects various parts of the middle ear to varying degrees, frequently leading to expansive ossicular chain destruction, hearing loss, otorrhea, dizziness, and intracranial complications. Cholesteatoma is a microsurgical challenge for the ear, nose and throat specialists. Recurrence is common even after successful surgical treatment, especially in childhood cases [1,2]
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