Expression Of HIF-1,VEGF And HSP90 In Middle Ear Cholesteatoma Epithelium And Their Possible Mechanism And Correlation In Middle Ear Cholesteatoma

Objective:Through examining the expression of hypoxia-inducible factor 1 alpha(HIF-1α),vascular endothelial growth factor(VEGF),heat shock protein 90 alpha(HSP90α)and heat shock protein 90 beta(HSP90β)in middle ear cholesteatoma epithelium,and to determine their possible role in the pathologic mechanism of the disease and correlation.Methods:22 patients with middle ear cholestatoma who were cured with mastoidotympanectomy elected in the Department of Otolaryngology and Head and Neck of The First Affiliated Hospital of Shanxi Medical University.The paraffin specimens and clinical records of 22 patients with middle ear cholesteatoma were collected.Ten normal skin specimens of external auditory canal from patients with middle ear cholesteatoma during operation were selected as the control group.The immunohistochemical two-step method was used to detect the distribution and expression of HIF-1α,VEGF,HSP90α and HSP90β in all samples.The average optical density was calculated by the computer image quantitative analysis system as the measurement result of the corresponding specimen.Results:1.HIF-1α,VEGF,HSP90α and HSP90β protein immunohistochemical positive staining in brown.HIF-1α and VEGF were expressed in the epithelium full-thickness skin of the middle ear cholesteatoma and the normal external auditory canal,the expression of basal layer was weak,and the main staining sites were in the cytoplasm,and some nuclei were also stained,while the staining was light in normal skin of the external auditory canal.HSP90α and HSP90β were expressed in the epithelium full-thickness skin of the middle ear cholesteatoma and the normal external auditory canal,and the main staining sites were in the cytoplasm,and some nuclei were also stained,while the staining was light in normal skin of the external auditory canal.2.The expression of HIF-1α,VEGF,HSP90α and HSP90β in middle ear cholesteatoma epithelium group was higher than that in normal external auditory canal skin group.The average optical density of HIF-1α in the two groups were0.0192±0.00869,0.0127±0.00289,the average optical density of VEGF in the two groups were 0.0175±0.00728,0.0072±0.00174,the average optical density of HSP90α in the two groups were 0.0252±0.00956,0.0144±0.00431,the average optical density of HSP90β in the two groups were 0.0302±0.01252,0.0125±0.00305.Independent sample t test was used for the comparison of each index between the two groups,and the differences between the two groups were statistically significant(P<0.05).3.The correlation of middle ear cholesteatoma group was analyzed by Pearson correlation analysis.The correlation coefficient between HIF-1α and VEGF in middle ear cholesteatoma epithelium was r=0.538,P=0.010,P<0.05,showing a significant positive correlation.The correlation coefficient between HIF-1α and HSP90β in middle ear cholesteatoma epithelium was r=0.431,P=0.045,P<0.05,showing a significant positive correlation.The correlation coefficient between VEGF and HSP90β in middle ear cholesteatoma epithelium was r=0.431,P=0.045,P<0.05,showing a significant positive correlation.While HIF-1α and HSP90α,VEGF and HSP90α,HSP90α and HSP90β,there is no correlation between each other(P>0.05).Conclusion:1.HIF-1α,VEGF,HSP90α and HSP90β were overexpressed in the epithelium of middle ear cholesteatoma,suggesting that they play an important role in the formation of middle ear cholesteatoma.2.The expression of HIF-1α and VEGF,HIF-1α and Hsp90β,and VEGF and Hsp90βin middle ear cholesteatoma epithelium are significantly correlated,suggesting that they may play a combined role in middle ear cholesteatoma.HIF-1α and HSP90α,VEGF and HSP90α,HSP90α and HSP90β,there is no correlation between each other.HSP90α could have contributed to the formation of cholesteatoma in different ways.