Expression of Apoptotic vs Antiapoptotic Proteins in Middle Ear Cholesteatoma

Abstract

Objectives To explore the role of antiapoptotic and apoptotic processes in the development of cholesteatoma by investigating the expression of an antiapoptotic (c-FLIP) and apoptotic (p53) protein relative to the expression of a proliferation marker (Ki-67). Study Design Basic science study. Setting Tertiary referral center. Subjects and Methods An immunohistochemical investigation was performed on 35 cholesteatoma specimens (21 acquired, 14 congenital) and 10 normal retroauricular skins to evaluate the expression of c-FLIP, p53, and Ki-67. The expression rate of each marker was measured to assess the difference between retroauricular skin and cholesteatoma, as well as between congenital and acquired cholesteatoma. Results c-FLIP expression was significantly higher in the cholesteatoma specimens than in retroauricular skin (P ˂ .05), while the expression of p53 did not significantly differ between the two. Ki-67 expression in cholesteatoma was significantly higher than in retroauricular skin (P ˂ .001). The c-FLIP expression rate was positively correlated with that of Ki-67 (r = 0.47, P = .001), and there was no significant correlation between the expression level of p53 and that of Ki-67 (r = 0.152, P = .319). In addition, no differences in c-FLIP, p53, and Ki-67 expression rates were evident between congenital and acquired cholesteatoma. Conclusions The upregulation of c-FLIP together with unchanged p53 suggests an altered equilibrium between apoptosis and antiapoptosis, favoring antiapoptosis, and may play a role in the pathogenesis of cholesteatoma.