Expression And Significance Of S-100, C-kit, HIF-1α, VEGF And TGF-β₁ In Primary Obstructive Megaureter

OBJECTIVETo clarify the expression of S-100 and C-kit and analyze the changes of gangliocytes and Interstitial cells of Cajal in Primary obstructive Megaureter.To study the expression and significance of HIF-1α,VEGF and TGF-β1 and explore pathogenesis of Primary obstructive Meganreter.METHOD25 specimens of the ureteral ending(ending group) and dilated segment(dilated group) were obtained from children with POM who were referred for surgery(aged 2 months to 10 years,mean 2.5 years),and they were divided into three groups:＜1y group,1～3y group and＞3y group.Control group:inferior segment of urete specimens were taken from 28 cases of renal neoplasm and tissues were confirmed histologically to be unaffected,and they were also divided into three groups:＜1y group,1～3y group and＞3y group.The samples were immunostained using antibodies specific for S100, C-kit,HIF-1α,VEGF and TGF-β1.Mean optical density(OD) of S-100,HIF-1α,VEGF and TGF-β1 staining in high microscope were calculated,and mean number of s-100 Positive gangliocytes and C-kit Positive Interstitial cells of Cajal were counted in high microscopic filed.Differences of mean number of s-100 Positive gangliocytes and C-kit Positive Interstitial cells of Cajal in high microscopic filed in ending group,dilated group and control group were evaluated using the t Test.Pearson's correlation coefficient was calculated to find the association between s-100 Positive gangliocytes and C-kit Positive Interstitial cells of Cajal.Regression lines were charted using SPSS 13.0 software to assess the correlation between the two cells(controls:(?)=-0.21+1.08x;ending group:(?) =-0.38+0.81x;dilated group:(?)=-1.94+1.33x;x:number of s-100 Positive gangliocytes;(?):number of C-kit Positive Interstitial cells of cajal).One-way ANOVA and the Least Significant Difference(LSD) statistical methods were used to analysis the changes of HIF-1α,VEGF and TGF-β1 in all study groups.RESULTSMean optical density of S-100 staining and mean number of s-100 Positive gangliocytes per microscopic filed were lower in ureteral endings compared to controls(P＜0.01) and dilated group(P＜0.01).The number of C-kit positive Interstitial cells of cajal was also significantly lower in ureteral endings compared to controls(P＜0.01) and dilated group(P＜0.01).No statistical significance was found between dilated group and control group.There was a Positive correlation between the number of gangliocytes and Interstitial cells of cajal in three groups.There were a line tendency between gangliocytes and Interstitial cells of cajal in three groups.Regression lines of the number of gangliocytes and Interstitial cells of cajal in three groups were charted using SPSS 13.0 software(ending group:(?)=-0.38+0.81x;dilated group:(?)=-1.94+1.33x; controls:(?)=-0.38+ 1.08x).The expression of HIF-1α,VEGF and TGF-β1 were slight or negative in controls, dilated group and＞3y ending group,but they were marked increased in＜1y ending group and 1～3y ending group.The statistic of F of mean optical density of HIF-1α, VEGF and TGF-β1 were 124.601,37.956,46.200.A global difference of all age groups were found,and there was a statistically significantly difference between any two groups except between＞3y group and control group.CONCLUSION S-100 positive gangliocytes and C-kit positive Interstitial cells of cajal play important roles and may have synergistic actions in Primary Obstructive Megaureter.Changing expression of HIF-1α,VEGF and TGF-β1 tightly participate in the pathogenesis of Primary Obstructive Megaureter.