Learning Objectives: Cholesteatoma is a destructive, potentially life-threatening lesion of the middle ear Cholestatoma tissue expresses tumor markers SERPINB3 and SERPINB4 Oncogenes like Lipocalin 2 are upregulated in Cholestatoma tissue, while tumor suppressor gene are downregulated.
Introduction: Cholesteatoma is a gradually expanding destructive epithelial lesion within the middle ear, which leads to extensive tissue destruction in the temporal bone followed by conductive and sensorineural hearing loss and facial nerve palsy. To develop new treatment strategies, gaining further insights into the complex gene regulation and signaling underlying the formation and progression of cholesteatoma are mandatory.
Methods: Gene expression profiling of cholesteatomas and regular external auditory skin from 17 patients via full genome micro-arrays containing 19,596 human genes followed by validation using real time PCR analysis.
Results: Full genome micro-arrays showed significantly increased expression of 811 genes in cholesteatoma tissue compared to regular external auditory skin, while 334 were found to be downregulated. Next to matrix metalloproteases MMP9, MMP10 and MMP12, the anti-apoptotic genes BCL2L1 and A20 were upregulated in cholesteatoma tissue. Providing a further linkage to tumorigenic tissue, expression of the tumor markers SERPINB3 and SERPINB4 as well as the oncogene Lipocalin 2 was increased in cholesteatoma tissue in comparison to external auditory skin. Accordingly, downregulation of the cell adhesion molecule cadherin 18 as well as the tumor suppressor gene inhibitor ID4 was observed in cholesteatoma tissue. Linking the characteristic expression of tumor-relevant genes in cholesteatoma to inflammation, the inflammation-related calcium binding protein S100A7A was found to be highly upregulated.
Conclusions: The Expression profile of cholesteatoma was found to be similar to a tumorigenic and chronically inflamed tissue, giving new insights in the complex biology of cholesteatoma.