The Significance Of MMP9 And VEGF Induces Angiogenesis In Middle Ear Cholesteatoma Proliferation

Objective:To observe the expression and significance of VEGF,MMP9,CD105 and Ki-67 in human middle ear cholesteatoma tissues and to investigate the correlation between their expression and the epithelial hyper- proliferation and development of cholesteatoma.The labeling index for Ki-67 was used to assess the proliferative activity and to examine the hyperproliferate state of keratinocyte in cholesteatoma tissues. The CD105 was used to label the microvessel in cholesteatoma tissues.Method:We examined the expression of VEGF,MMP9,CD105 and Ki-67 by immunohistochemical staining in 45 samples from middle ear cholesteatoma and 10 epithelial cells samples from the external auditory meatus. The computer image quantitative analysis was used to examin the expression of VEGF,MMP9, and Ki-67. The microvasculars of cholesteatoma were measured by MVD which were immunohistostained with CD105.Result:1.The microvasculars of cholesteatoma matrix were plentiful and close.But the microvasculars of the skin of external acoustic meatus were less and more raritas than cholesteatoma.The mean MVD was 28.3±7.7(n=45) in cholesteatoma and 6.1±2.5(n=10)in the skin of external acoustic meatus.There were statistical significance between the two groups(t=8.905,p<0.001).2.The the expression of VEGF,MMP9 in cholesteatoma and in normal skin epithelial tissues: The positive immunohistostaining of MMP9 and VEGF appeared all the layers, MMP9 and VEGF protein was localized mostly in the cytoplasm,and it showed the tendency of gradual increasing from basal layer to corneous layer. The normal skin epithelial tissues showed weakly positive.The results showed that VEGF in cholesteatoma tissues (91.43%) was higher than that in normal skin epithelial tissues (40.00%), the expression level of VEGF in cholesteatoma tissues was significantly increased (P<0.01). The results also showed that MMP9 in cholesteatoma tissues (68.57%) was higher than that in normal skin epithelial tissues (20.00%), the expression level of MMP9 in cholesteatoma tissues was significantly increased (P<0.01). The expression of MMP9 and VEGF was present positive correlation in cholesteatoma tissues (P<0.05).3. The results showed that Ki-67 in cholesteatoma tissues (64.44%) was higher than that in normal skin epithelial tissues (20.00%),the expression level of Ki-67 in cholesteatoma tissues was significantly increased(P<0.01). With the increased of mean MVD, the expression level of Ki-67 in cholesteatoma tissues increased.Conclusion:1,there were microvascular proliferation in the presence of cholesteatoma tissues.2,More cells in cell cycle and the strong proliferation activity in cholesteatoma epithelium. Microvascular proliferation can be highly abnormal proliferation of cholesteatoma epithelium provide rich blood supply and nutrition, the high proliferation of epithelial cells in cholesteatoma cholesteatoma matrix dependent on microvascular.3,VEGF and MMP9 protein plays an important role in human middle ear cholesteatoma proliferation. Correlation analysis showed that VEGF and MMP9 in the induction of angiogenesis has a synergistic effect.