Study On Expression Of ET-1,VEGF And Their Correlations With Angiogenesis In Epithclial Ovarian Neoplasms

Objective: Ovarian cancer is one of the most common malignant tumor in the Gynecologic tumor.The mortality of ovarian cancer is the highest among all the gynecologic tumors because of its indistinct clinical symptoms.and we can not make a diagnosis during the early stage.So the paitents with ovarian cancer are poor prognosis,Although Traditional treatments make a progress,the prognosis of ovarian cancer still remain poor.Study have approved that angiogenesis plays a key role in the development and metastacis of solide tumor,and angiogenesis may be correlated with ascite formation in ovarian cancer.Tumor and host also can produce many angiogenesis factors,which act on each other and play a role in all process of tumorigenesis.VEGF is by far the most important specific factor that elicits the angiogenesis. VEGF ,through the binding with VEGF receptor,induce a series of reaction. ET-1 plays a role in all process of tumorigenesis.ET-1 may act in synergism with VEGF in the angiogenesis of ovarian tumor .To investigate the expression of ET-1,VEGF and their correlations with angiogenesis in epithelial ovarian neoplasms,for clear understanding the state of angiogenesis which may provide a new idea for antagonizes therapy of ovarian tumor.Methods:All the specimens were collected from the patients with ovarian cancer who were treated firsrt in the Gynecology department of the Fourth Affiliated Hospital of Hebei Medical University from April 2005 to October 2006.All the epithelial ovarian cancer were confirmed by pathologic observation.46 epithelial ovarian cancer and 14 benign ovarian tissue were recruited.sixty samples of epithelial ovarian neoplasm tissues were examined for ET-1 and VEGF protein expression by immunohistochemistry streptavidin-peroxidase method,including 14 cases cystadenoma and 41cases ovarian cancer.The new growth endoangiogen cell was marked with FVIII-RA monoAb.The microvessel density of tumor was calculated by microscopy.The expression of ET-1 protein ,Apoptosis ratio and proliferation index were detected by FCM in 36 epithelial ovarian tumors.Results: 1 The primary immunostaining location of ET-1 was cytoplasm.The positive rate of ET-1 protein was 14.28%,69.56% in benign and malignant ovarian tumor tissues respectively.The positive rate in ovarian cancer was significantly difference than in cystadenoma(P<0.05). The positive rate of ET-1 protein was 50%,81.82% in different histological grade of epithelial ovarian cancer . The positive rate in Grade1-2 was significantly difference than in Grade3(P<0.05). The expression of ET-1 protein was no significantly associated with age,FIGO stage,pathological type(P>0.05). 2 The positive rate of VEGF protein was 14.28%,60.87% in benign and malignant ovarian tumor tissues respectively.The positive rate in ovarian cancer was significantly difference than in cystadenoma(P<0.05). The positive rate of VEGF protein was 41.67%,90.91% in different histological grade of epithelial ovarian cancer . The positive rate in Grade1-2 was significantly difference than in Grade3(P<0.05). The positive rate of VEGF protein was 25%,73.68% in different FIGO stage of epithelial ovarian cancer . The positive rate in FIGO I-II was significantly difference than in FIGO III-IV(P<0.05). The expression of VEGF protein was no significantly associated with age,pathological type(P>0.05).3 The MVD of cystadenomas was lower than that of ovarian carcinoma, There were significant differences between them (P<0.05). The MVD of mucinous ovarian carcinoma was much higher than that of serous type and endometrioid type(P<0.05, P<0.05). The value of MVD was significantly associated with FIGO stage.The expression of MVD was no significantly associated with age,histological grade (P>0.05).4 Spearman rank correlation analysis is showed that there was a positive correlation between VEGF and ET-1 (P<0.05).The same result was found between VEGF, ET-1 and MVD( P<0.05) .5 FCM was performed to examine the expression of ET-1 protein of 15 epithelial ovarian cancer,15 mucinous cystadenoma and 6 borderline cystadenoma.There are significantly difference were observed among them(P<0.05).The expression of ET-1 protein in Grade3 was higher than that in Grade1-2(P<0.05).6 The apoptosis ratio of epithelial ovarian cancer,munious cystadenoma ,borderline cystadenoma were(19.46±7.16) ,(14.46±4.17),(14.33±5.28). There were significant differences between them.The proliferation index of epithelial ovarian cancer,munious cystadenoma,borderline cystadenoma were(0.93±0.22),(0.87±0.11), (0.89±0.22).Conclusions: 1 The expression level of ET-1 and VEGF protein in epithelial ovarian cancer was significantly higher than in munious cystadenoma and borderline cystadenoma.This result suggested that ET-1 and VEGF might be act on the growth and angiogenesis of ovarian carcinoma.2 The value of MVD in epithelial ovarian cancer was significantly higher than in munious cystadenoma and borderline cystadenoma. The value of MVD was significantly associated with FIGO stage.This result suggested that MVD might contribute to the processes of tumor cell invasion and metastasis which suggested poor survival of ovarian cancer patients.3 The expression of ET-1,VEGF protein had positive relation with MVD in ovarian carcinoma.The protein expression of ET-1 and VEGF were positive correlated. It is suggested that the co-expression of ET-1 and VEGF seems to play a key role in the process of angiogenesis. 4 The expression of Apotosis ratio and Proliferation index in epithelial ovarian cancer were higher than munious cystadenoma and borderline cystadenoma.There are significantly difference between Grade1-2 and Grade3 in epithelial ovarian cancer.