Expression And Significance Of VEGF-C In Endometriosis

Objective:In this study,we investigated the expreesion of vascular endothelial growth factor C(VEGF-C) in the tissues and the serum of the patients with endometriosis,the therapeutic effects of Endostar in the rat endometriosis model.The study aims to hope VEGF-C to become a new and potentialtherapeutic target in endometriosis.Methods:(1)By detecting the protein expression of VEGF-C in endometriosis tissues using immunohistochemical methods in endometriosis tissues microarray to explore the correlationship betweem VEGF-C and endometriosis.(2)Using the characteristics of extraccellular secreted protein that can be dtectded in the serum,We determined VEGF-C serum concentration in patients endometriosis(n=86) and benign ovarian cyst(n=36)and the healthys(n=40)by ELISA.Then we evaluate its clinical diagnostic significance.(3)By establishing the rat endometriosis modle,we observed the effects of endostatin(ES)-Endostar in the size and weight of the rat endometriosis plate.Then we observed the diffence of ectopic endometrium tissues and the expression of VEGF-C in treatment group and control group using HE staining and immunohistochemical analysis in order to evaluate the therapeutic effects of Endostar as antiangiogenic target.It may provided the clinical evidences for the anti-angiogenic treatment of endometriosis.Results:(1)Immunohistochemical expression of VEGD-C was higher in endometriotic tissues than in benign ovarian cyst tissues(p<0.0001).The high expression of VEGF-C in endometriotic tissues was 69.88% while in benign ovarian cyst was10%.58.70% lesions staged grade I-II were high VEGF-C expression and 83.78% lesions staged grade III-IV were high VEGF-C expression.Expression of VEGF-C was higher in the endometriosis grade III-IV than in endometriosis grade I-II(p=0.013).The high exprression of VEGF-C in secretory phase was 75.0%,while in proliferative phase was65.96%.Data showed that was no difference between two menstrual phase(p=0.374)as well as serum CA125(p=0.188).The expression of VEGF-C in serum CA125 ≥35 U/ml was75.0%,while in CA125<35 U/ml was 61.29%.(2)In the group of healthy human,patients with other benign ovarian cyst and patients with endometriosis,the serous VEGF-C average concentration detected by ELISA were 35.79±15.07pg/ml(14.05-69.57pg/ml),37.03±24.08pg/ml( 10.14-111.88pg/ml), 64.25±57.20pg/ml( 9.99-287.95pg/ml),respectively.The serous concentration of VEGF-C in serum CA125 ≥35 U/ml group and in serum CA125 < 35 U/ml group were64.49±58.45pg/ml(9.99-287.95pg/ml),62.61±50.32pg/ml(10.46-160.47pg/ml)。There was significantly difference among healthy human,patients with other benign ovarian cyst and the endometriosis group,P value was 0.0000372 to healthy group and 0.00037 to patient with benign ovarian cyst group,while P value was 0.7949 between healthy group and patient with other benign ovarian cyst group,respectively.P value was 0,9114 between serum CA125 ≥35 U/ml group and serum CA125 <35 U/ml group.The results of ROC curve displayed that if we diagnose high risk endometriosis by serum VEGF-C concentration,the Area Under Curve(AUC)was 0.615±0.049.The critical value of diagnosis was 62.98pg/ml determined by Youden’s index,with 39.5% and 95.0% of sensitivity and specificity,respectively.(3).There was a significant reduction in the mean implant volume per rat in the treatment group(8.57±3.10mm3)as compared with the control group( 37.90±18.50mm3)(p=0.0435).And also was a significant reduction in the mean implant weight per rat in the treatment group(0.0568±0.020231mm3)as compared with the control group( 0.1184±0.014291mm3)( p=0.001527);We observed ectopic endometrium was significantly reduced in treatment group compared with control group by HE staining as well as the expression of VEGF-C.Conclusion:1.VEGF-C maybe involve in the endometriosis progression,besides,it also has relevance with the endometriosis severity.2.VEGF-C may be used as a new serological marker of endometriosis diagnosis3.Endostatin that is an endogenous inhibitors of angiogenesis had effection in rat endometriosis modle.4.VEGF-C might be a potential theraputic target for endometriosis.