The Study Of The Relationship Between The Expression Of VEGF-C And VEGF-D And Peri-cancer Lymphangiogenesis And Lymphatic Metastasis In Epithelial Ovarian Carcinoma

Objective:1. To study the expression of vascular endothelial growth factor C(VEGF-C) and vascular endothelial growth factor D(VEGF-D) in human epithelial ovarian carcinoma.2. To study the relationship between the expression of VEGF-C and VEGF-D and lymphatic vessel density(LVD) and lymph node metastasis in epithelial ovarian carcinoma. Our target is to explore the role of lymphangiogenesis in metastasis of epithelial ovarian carcinoma.Methods: 1. The expression of VEGF-C and VEGF-D proteins in 32 benign cystadenomas and 11 borderline tumors and 44 epithelial ovarian carcinomas was detected by immunohistochemistry, as well as expression of vascular endothelial growth factor receptor 3 (VEGFR-3) and CD34 proteins in ovarian carcinomas, followed by light microscopic examination. Counting of LVD and microvessel density (MVD) was performed.2. The expression of VEGF-C and VEGF-D and VEGFR-3mRNA in 8 benign cystadenomas and 21 ovarian carcinomas was detected by RT-PCR, and the results were analyzed by gel imaging system. Enzyme-histochemistry staining and LVD counting were performed in epithelial ovarian carcinoma tissue.3. Correlation was analyzed between the expression of VEGF-C and VEGF-D and VEGFR-3 and clinicopathological characteristics such as LVD, lymph node metastasis and peritoneal metastasis.Results:1. VEGF-C and VEGF-D were both expressed in benign and borderline and malignant ovarian tumors, and positive staining was located in cytoplasm of tumor cells. Their expression was apparently higher in ovarian carcinomas than in borderline(P<0.05 and P<0.001 respectively) and benign(P<0.05 and P<0.001 respectively) ovarian tumors, and their expression levels were obviously relevant to peritoneal metastasis, lymph node metastasis and clinic staging(P<0.05 or P<0.01). There was no obvious difference between the expression of VEGF-C and VEGF-D in benign tumors and borderline tumors(P>0.05). The expression of VEGF-C was positively relevant to VEGF-D in malignant, borderline and benign tumors(r=0.674,P<0.01; r=0.683,P<0.05; r=0.703,P<0.01).2. Positive staining of VEGFR-3 was located in ovarian carcinoma cells and endothelium cells of vessels, and its expression level was positively relevant to the expression of VEGF-C and VEGF-D and lymph node metastasis(P<0.01 respectively). LVD was positively relevant to peritoneal metastasis, lymph node metastasis and clinic staging(P<0.01 respectivly), and to the expression of VEGF-C and VEGF-D(P<0.001 respectively). MVD was positively relevant to peritoneal metastasis(P<0.05),distant metastasis(P<0.001), clinic staging(P<0.01)and the expression of VEGF-C(P<0.05).3. The mRNA expression of VEGF-C and VEGF-D and VEGFR-3 was obviously higher in ovarian carcinomas than in benign ovarian tumors, and Statistical difference existed in these two kinds of results(P<0.01 or P<0.05);The mRNA expression of Flt-4 was significantly correlated with the mRNA expression of VEGF-C and VEGF-D( P<0.05 and P<0.01 respectivly),and the two latter markers were significantly correlated with each other(P<0.05).4. LVD in ovarian carcinoma tissues of positive expression of VEGF-C and VEGF-D mRNA was apparently higher than those of negative expression of VEGF-C and VEGF-D mRNA, and there was significant difference in these two groups(P<0.05 and P<0.01 respectively);LVD in peri-carcinoma tissues with lymph node metastasis was apparently higher than those with no lymph node metastasis, and there was significant difference between them(P<0.001).conclusion:1. Up-regulation of VEGF-C,VEGF-D and VEGFR-3 was obviously relevant to peri-carcinoma LVD and lymph node metastasis, which indicate binding of VEGF-C and VEGF-D with VEGFR-3 could facilitate the peri-tumor lymphangiogenesis and lymphatic metastasis, which is possibly associated with occurrence and differentiation of tumor.2. Peri-tumor lymphangiogenesis mediated by VEGF-C and VEGF-D not only resulted in lymphatic diffusion but also correlated with direct diffusion ,and these lymphatics might be targets of thera...