Abstract: Objective: To observe the expression of cyclindependent kinase4(CDK4) and cyclindependent kinase inhibitor P16 in human middle ear cholesteatoma and to explore their roles in the development of cholesteatoma. Methods: Thirtyfive cholesteatomas tissues and twenty normal human external ear canal skin were used in this study. All specimens were stained by an immunohistochemical SABC method to detect the expression of CDK4 and P16. Correlations between the above indexes and between the above indexes and the degree of ossicular destruction were investigated. Result: CDK4 and P16 were expressed in parabasal layers and the upper layer, mainly in the prickle and granular layers of cholesteatoma epithelium. Their positive rates were 68.6% and 88.6%, respectively. Statistical analysis showed that there was a significant difference in positive rates between the normal external ear canal epithelium and the cholesteatoma epithelium（P=0.011, P=0.02）, and a positive correlation between CDK4 and P16 in the cholesteatoma group(P＜0.05). The statistical results indicated that the expression of CDK4 and P16 did not related to the extent of ossicular damage in cholesteatoma(P＞0.05). Conclusion： CDK4 and P16 are overexpressed in human middle ear cholesteatoma epithelium and positively correlate with each other, suggesting that they play a cooperative role in the development of cholesteatoma. The cholesteatoma epithelium has a hyperproliferation ability and a mechanism of inhibiting the proliferation. The result of immunohistochemical examination is not related to the degree of ossicular destruction.

Key words: P16, CDK4, Cholesteatoma, middle ear, Immunohistochemistry