Study On The Expression Of VEGF-C And Its Correlation With Metastasis In Ovarian Epithelial Tumors

Invasion of lymphatic vessles by tumour cells and subsequent development of lymph node metastases significantly influences prognosis of ovarian epithelial tumour patients. It is well established that angiogenesis, the formation of new blood vessels,is necessary for the growth and metastatic spread of solid tumours, and tumour induced lymphangiogenesis, the formation of new lymphatic vessels, has been recently considered important for metastatic spread and prognosis of malignant tumours. Vascular endothelial growth factor-C ( VEGF-C ) is a member of the VEGF superfamily, and involves physiological and pathological lymphangiogenesis and angiogenesis via vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3. VEGF-C play a important role in lympatic metastasis.VEGFR-3 belongs to the VEGF tyrosine kinase receptor family , is expressed predominantly in the endothelium of lymphatic vessels, and has been proposed to be a specific molecular maker for lymphatic endothelial cells.Theendothelial marker CD31(PECAM-1) is expressed by endothelium of both lymphatic and blood vessel. A positive association between of VEGF-C protein levels with lymph node metastasis has been found in a variety of carcinomas including prostate , lung, stomach and esophagus etc. Relatively little is known, however,about the relationship between VEGF-C expression and lymphangiogenesis, angiogenesis and lymphatic metatasis in epithelial ovarian tumors.Aim and objectiveAim: To explore the role of VEGF-C in the process of angiogenesis ,lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors.Objective:(1) To study the expression of VEGF-C, VEGFR-3 and CD31 expression in epithelial ovarian tumors. (2) To investigate the expression of between VEGF-C , VEGFR-3 and CD 31 in epithelial ovarian carcinomas and its relationship with tumor metastasis.Methods(1) The expression of VEGF-C mRNA was examined by in situ hybridization in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign cystadenomas.(2) Immunohistochemical staning for VEGF-C,VEGFR-3 and CD 31 was performed in epithelial ovarian carcinomas, borderline tumors and benign cystadenomas.(3) VEGFR-3 positive vessels and microvessel density (MVD) were assessed by the image analysis.Results(1) VEGF-C mRNA and protein expression in epithelial ovariantumors:VEGF-C mRNA and protein expression was detected within cytoplasm of carcinoma cells.Of the 30 epithelial ovarian carcinomas , thirteen (43.33%) and seventeen(56.67 % ) showed positive VEGF-C mRNA and protein expression, respectively. VEGF-C protein expression in ovarian epithelial carcinomas was significantly higher than that in borderline tumors(P < 0.05).Benign cystadenomas showed no cytoplasmic staning for VEGF-C protein.(2) VEGFR-3 and CD31 expression in epithelial ovarian tumors: VEGFR-3 is expressed in the endothelium of lymphatic vessels adjacent to the carcinoma, and CD31 is expressed by endothelium of both lymphatic and blood vessel in the resection specimens(MVD). Both VEGFR-3 positive vessels and MVD in ovarian epithelial carcinomas were higher than those in borderline and benign tumors(P<0.05), but there was no significant difference in in borderline and benign tumors(P>0.05).(3) The relation between expression of VEGF-C,VEGFR-3 and CD 31 and clinicopathological factors: In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were higher in the cases of clinical stage III-IV and with lymphatic metastasis than those of clinical stage I -II and without lymphatic metastasis respectively (p<0.05) . There were no significantly differences between VEGF-C protein expression, VEGFR-3 positive vessels, MVD and histological type, histological grade(differentiation) in ovarian epithelial carcinomas(P>0.05).(4) The relationship between VEGF-C expression , VEGFR-3 positive vessels and MVD in epithelial ovarian carcinomas: VEGFR-3 positive vessels and MVD was significantly higher in the VEGF-C p...