Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity

Abstract

Objectives Cholesteatoma is a nonneoplastic destructive lesion of the temporal bone with debated pathogenesis and bone resorptive mechanism. Both molecular and cellular events chiefly master its activity. Continued research is necessary to clarify factors related to its aggressiveness. We aimed to investigate the expression of Ki-67, cytokeratin 13 (CK13) and cytokeratin 17 (CK17) in acquired nonrecurrent human cholesteatoma and correlate them with its bone destructive capacity.Methods A prospective quantitative immunohistochemical study was carried out using fresh acquired cholesteatoma tissues (n=19), collected during cholesteatoma surgery. Deep meatal skin tissues from the same patients were used as control (n=8). Cholesteatoma patients were divided into 2 groups and compared (invasive and noninvasive) according to a grading score for bone resorption based upon clinical, radiologic and intraoperative findings. To our knowledge, the role of CK17 in cholesteatoma aggressiveness was first investigated in this paper.Results Both Ki-67 and CK17 were significantly overexpressed in cholesteatoma than control tissues (P<0.001 for both Ki-67 and CK17). In addition, Ki-67 and CK17 were significantly higher in the invasive group than noninvasive group of cholesteatoma (P=0.029, P=0.033, respectively). Furthermore, Ki-67 and CK17 showed a moderate positive correlation with bone erosion scores (r=0.547, P=0.015 and r=0.588, P=0.008, respectively). In terms of CK13, no significant difference was found between cholesteatoma and skin (P=0.766).Conclusion Both Ki-67 and CK17 were overexpressed in cholesteatoma tissue and positively correlated with bone resorption activity. The concept that Ki-67 can be a predictor for aggressiveness of cholesteatoma was supported. In addition, this is the first study demonstrating CK17 as a favoring marker in the aggressiveness of acquired cholesteatoma.

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“…That probably might suggest the specific stage of disease with a decrease in cellular activity. However, this data was different from other studies where Chung et al[35] and Hamed et al[36] proved overexpression of Ki-67 in cholesteatoma tissue compared to skin epithelium. This might be explained by the fact that Hamed and other authors took control skin from the same patients, who had cholesteatoma.…”

The Allele 2 of the VNTR Polymorphism in the Gene That Encodes a Natural Inhibitor of IL-1β, IL-1RA Is Favorably Associated With Chronic Otitis Media

“…Hereof we investigated its copy number variant with regard to cholesteatoma in patients with COM and we show the significant difference in allele frequency, with allele 2 predominance in COM patients with cholesteatoma. Molecular mechanisms and genetic basis of both, COM and cholesteatoma and their potential clinical aggressiveness are challenging subject in current research [ 33 ] and has yet to be resolved. Recently, an extensive review was published in order to gather existing literature regarding heritability of cholesteatoma [ 34 ].…”

Cholesteatoma Pearls: Practical Points and Update

“…Studies evaluating markers as indicators of the aggressive nature and bone destruction capacity have recently shown that some cholesteatomas overexpress Ki-67, a cell proliferation marker of tumors and non-neoplastic proliferative disorders that includes cholesteatoma. CK17, a marker of keratinocyte differentiation, has been shown to be a predictor of aggressiveness and invasive capability when present [45]. Hamed et al observed that overexpression of both markers were seen in the epithelial portion of cholesteatoma in cases of invasive cholesteatoma where severe ossicular destruction was present whereas, the non-invasive group expressed each marker in an inactive form [45].…”

“…CK17, a marker of keratinocyte differentiation, has been shown to be a predictor of aggressiveness and invasive capability when present [45]. Hamed et al observed that overexpression of both markers were seen in the epithelial portion of cholesteatoma in cases of invasive cholesteatoma where severe ossicular destruction was present whereas, the non-invasive group expressed each marker in an inactive form [45].…”