The importance of Kİ-67, CK-6 and CK-16 expression in the Cholesteatoma and their correlation with its destructive effect and hyperproliferative capacity

Objective: Cholesteatoma, with its hyperproliferative feature and destructive pathogenesis, leads to bone destruction of middle ear structures and surrounding areas. We aimed to investigate the expression of Ki-67, cytokeratin-6 (CK-6) and cytokeratin-16 (CK-16) in acquired and recurrent cholesteatoma and to show the relationship with bone destructive capacity. Material and Method: A prospective study was conducted on 45 cholesteatoma tissues and 10 external ear canal skins collected during the tympanoplasty operation between February 2015 - September 2018 in Gaziantep University Medical Faculty Department of Otorhinolaryngology. Whether the cholestesteatoma was recurrent or not, the extent of cholesteatoma during the operation, ossicular damage and the presence of complications were recorded. The patients were divided into four groups: Complicated cholesteatoma, recurrent cholesteatoma, uncomplicated cholesteatoma, and the external ear canal skin as control group. Groups were compared in terms of Ki-67 expression level, CK-6 and CK-16 staining patterns. Results: Ki-67 index was significantly higher in all cholesteatoma groups compared to control group. In addition, Ki-67 index was significantly higher in the complicated and recurrent cholesteatoma groups than uncomplicated group (p=0.015 and p=0.001, respectively). CK-6 showed only suprabasal layer staining of the external ear canal skin, wherease showed all layer staining pattern in cholesteatoma. CK-16 showed basal-suprabasal staining in the external ear canal skin but stained the suprabasal layer as pale. Additionally, CK-16 showed basal-suprabasal (n=14) and all layer (n=31) staining pattern in cholesteatoma. When the cholesteatoma groups were compared in terms of CK-16 staining pattern, the only significant result was higher full-coat staining rates in the recurrent cholesteatoma group compared to the uncomplicated cholesteatoma group (p = 0.022). Conclusion: Ki-67 index has been shown to be an important pathological parameter in the evaluation of aggressive behavior of cholesteatoma. In addition, our study is the first study showing the significant association of Ki-67 and CK-16 with recurrent cholesteatomas. Key words: Recurrent cholesteatoma, Complicated cholesteatoma, Cytokeratin-6, Cytokeratin-16, Ki-67