Evaluation Of CYLD, C-jun And Ki-67in Middle Ear Cholesteatoma Epithelium And Its Significance

Objective: To analyze the expression of the tumor suppressor gene CYLD(cylindromatosis), the proto-oncogene c-jun and the proliferating cell nuclear antigenKi-67in middle ear cholesteatoma epithelium, explore the correlation between theirexpressions and investigate the possible roles of CYLD, c-jun and Ki-67in thepathogenesis of middle ear cholesteatoma.Methods: Immunohistochemical technique was used to detect the expression of CYLD,c-jun and Ki-67in samples of middle ear cholesteatoma tissue from30patients, insamples of middle ear granulation tissue from20patients and in specimens of normalretroauricular skin from20of them.Results: The expression of CYLD protein was mainly in the basal layer cells of middleear cholesteatoma epithelium. The positive rate of CYLD protein expression in middle earcholesteatoma epithelium was26.7%, this rate in normal retroauricular skin was85%, andthe former was significantly lower than the latter(2=16.333, P=0.000). However, the ratein middle ear granulation tissue was20%, there were no significant difference inexpression levels between middle ear cholesteatoma tissue and middle ear granulationtissue (2=0.041, P=0.839). The expression of c-jun protein was almost in all cells of theepithelial layers of middle ear cholesteatoma epithelium. The positive rate of c-jun proteinexpression in middle ear cholesteatoma epithelium was80%, this rate in normalretroauricular skin was25%, and that in middle ear granulation tissue was30%. The ratein middle ear cholesteatoma epithelium was significantly higher than that in normalretroauricular skin (2=14.901,P=0.000) and it was also significantly higher than that inmiddle ear granulation tissue (2=12.500, P=0.000).The expression of Ki-67protein wasalmost in all cells of the epithelial layers of middle ear cholesteatoma epithelium. Thepositive rate of Ki-67protein expression in middle ear cholesteatoma epithelium was73.3%, this rate in normal retroauricular skin was20%, and that in middle ear granulationtissue was30%. The rate in middle ear cholesteatoma epithelium was significantly higherthan that in normal retroauricular skin (2=13.675, P=0.000) and it was also significantlyhigher than that in middle ear granulation tissue (2=9.145, P=0.002). Using Spearman’s rank correlation test, we found that there was a negative correlation between CYLD andc-jun protein expression in middle ear cholesteatoma epithelium (rs=-0.401, P=0.028),while, there was no significant correlation between CYLD and c-jun protein expression inmiddle ear granulation tissue (rs=-0.003, P=0.991).Conclusion: Middle ear cholesteatoma epithelium has a higher proliferative capacitycompared to the middle ear granulation tissue and the normal retroauricular skin. Theabnormal expression of CYLD, c-jun and Ki-67in middle ear cholesteatoma epitheliumsuggests their important roles in the formation and development of cholesteatoma. CYLDnegatively regulates c-jun expression may contribute to the formation and development ofmiddle ear cholesteatoma.