Expression And Significance Of Apoptosis Inhibitory Proteins Livin And Survivin In Human Middle Ear Cholesteatoma Epithelium

Background and ObjiectiveCholesteatoma is due to the stratified squamous epithelium of the tympanic membrane and external auditory canal piercs into the middle ear cavity and the accumulation of the mass,the outer layer of it is surrounded by fibrous tissue containing deciduous epithelial,cutinized mass and cholesterol crystal,and the exact mechanism of its form is not clear yet,though there are two theories,one is the pocket invagination doctrine and the other is epithelial immigration doctrine.In the past 10 years,more and more attention were paid to the role of a variety of cytokines in the pathogenesis of cholesteatoma otitis media.Recently,researchers believed that the incidence of cholesteatoma otitis media was an imbalance in the process of cell proliferation and apoptosis,and some researchers reported that lots of cholesteatoma were found to have relationship with abnormal apoptosis and abnormal cytokine expression.In this research we study the expression of the Livin and Survivin in the tissue of Cholesteatoma and normal external auditory canal skin,To investigate the relationship of the expression of Livin,Survivin and the cholesteatoma otitis media, and to explore the correla tion of the Livin and Survivin,and the possible mechanisms in the pathogenesis of middle ear cholesteatoma,and to provide a theoretical basis for treatment.MethodsAccording to the standards,we selected 25 cases of cholesteatoma otitis media patients from the ENT department in 1^st Affiliated Hospital of Jinan University as experimental group,collected 25 surgical resection specimens,and at the same time to select 15 cases of bone with external auditory canal skin in these patients as a control group,collected 15 normal skin samples of the external auditory canal.All specimens required to formalin-fixed,paraffin-embedded.Each of the experimental specimens were done with hematoxylin and eosin staining to determine the pathological diagnosis.Detecting the expression of Livin and Survivin in 25 cases of middle ear cholesteatoma(cholesteatoma group) and 15 cases of external auditory canal skin and bone tissue(control group) by using two-step immunohistochemical,and using terminal transferase-mediated in situ nick end labeling staining(TUNEL) to detect the apoptosis status of both tissues and to analyze the correlation between them. SPSS 13.0 system was used to perform the statistical analysis.Result1,There were 5 patients in 25 cases of cholesteatoma specimens had positive expression of Livin,Livin-positive cells was observed in basal,upper-basal cells, among them 4 cases were+,1 case was++,20 cases were negative.15 cases of the normal external auditory canal skin samples had 9 cases of positive expression of Livin protein,6 cases were negative.Livin expression and the intensity of the expression in cholesteatoma epithelium significantly reduced compared with normal external auditory canal skin,and the difference had statistical significance(a=0.05,P＜0.01).2,There were 7 patients in 25 cases of cholesteatoma specimens had positive Survivin protein expression,it expressed in the nuclei and(or) cytoplasm of the basal and upper-basal layers of the cholesteatoma epithelium,among them 6 cases were+, 1 case was++,18 cases were negative.15 cases of the normal external auditory canal skin samples had 10 cases of positive expression of Survivin protein,5 cases were negative.Compared with the control group,Survivin expression and the expression intensity in cholesteatoma epithelium significantly reduced,the difference had statistical significance(a=0.05,P＜0.01).3,By using Spearman rank correlation analysis to analyze the expression of Survivin and Livin in the cholesteatoma epithelium,using Kappa analysis to check regularity.The expression of Survivin and Livin in the cholesteatoma epithelium was positively correlated,and the regularity was fairly fine(r_s=0.749,P=0.000, Kappa=0.688).4,The apoptosis status of cholesteatoma epithelium was significantly higher than normal epithelium,the expression of Survivin and Livin was negatively correlated with apoptosis.Conclusion1,The expression of apoptosis inhibitory proteins Livin and Survivin were significantly reduced in Cholesteatoma,and they were closely related to the apoptosis of the cholesteatoma epithelium,suggested that Livin and Survivin might be involved in the regulation of apoptosis process of the cholesteatoma epithelium,which play an important role in the occurrence and development of cholesteatoma.2,The expression of apoptosis inhibitory proteins Livin and Survivin was positively correlated in cholesteatoma,they might cooperate in the occurrence and the development of cholesteatoma.3,Apoptosis inhibitory proteins Livin and Survivin and apoptosis was a negative correlation,adjust the expression of apoptosis inhibitory proteins Livin and Survivin might be a new way to treat the cholesteatoma otitis media.