The Relationship Of The Expression Of VEGF-C, Angiogenesis And Lymph Angiogenesis In Pancreatic Carcinomasand Lymphatic Metastasis

Objective: Vascular endothelial growth factor C (VEGF-C) has angiogenic and lymphangiogenic properties and is associated with the development of lymphatic metastases in a number of epithelial malignancies that has been implicated in several human solid tumors. However, the clinical significance of VEGF-C has remained unknown in pancreatic carcinoma. The aim of this study was to determine VEGF-C protein expression in a series of pancreatic carcinomas and to investigate the relationship of the expression of VEGF-C and its receptor VEGFR-3 with angiogenesis and lymphangiogenesis in pancreatic carcinomas. Methods: Paraffin-embedded tumor specimens including pancreatic carcinoma tissues and paracarcinoma tissues of 37 surgically resected pancreatic carcinoma and 10 cases of normal pancreatic tissue were immunohistochemically stained for VEGF-C and VEGFR-3. The correlations among VEGF-C expression, VEGFR-3 expression, microvessel density (MVD), lymphatic vessel density (LVD) and clinicopathologic features were statistically analyzed.Results: VEGF-C expression was observed in the cytoplasm of carcinoma cell. Comparisons of the primary tumors with paracarcinoma and normal pancreatic tissues showed that there was a significant upregulation of VEGF-C. But there was no significant difference between that of paracarcinoma with normal pancreatic tissues. VEGF-C expression was significantly correlated with lymph node metastasis and tumor stage. No correlation was found between the VEGF-C expression with tumor grade, tumor diameter, patient age and gender. Twenty-one (56.8%) of the 37 pancreatic carcinomas were highly positive for VEGFR-3 protein by immunohistochemistry. VEGFR-3 expression was significantly correlated with lymph node metastasis and tumor histological grade. Statistical analysis further showed that there was no significant correlation between VEGFR-3 with patient age and gender, stage and tumor size.There was different MVD in normal pancrease tissue (11.60±3.65), paracarcinoma tissue (13.14±4.42) and that in tissue of pancreatic carcinomas (22.49±7.84).And the LVD was 16.38±6.53 in paracarcinoma tissue, which is higher than that of normal pancrease tissue(8.60±3.16). But we hadn't found lymphatic in pancreatic carcinomas tissues.LVD and MVD of tumors with lymph node metastasis was higher than those of tumors without lymph node metastasis. There was significantly different MVD and LVD between Ⅰ-Ⅱ stage and Ⅲ-Ⅳ stage, among different tumor histological grade. MVD correlated with tumor size.. But no correlation between LVD and MVD and patient age and gender had been found. Tumors with higher VEGF-C/VEGFR-3 expression showed significantly higher MVD/LVD than tumors with lower expression of VEGF-C/VEGFR-3Conclusion:The broad expression of VEGF-C and VEGFR3 in pancreatic carcinomas suggests involvement in tumor lymph angiogenesis, promoting tumor growth and propagation of cancer cells. Though angiogenesis is not associated with the expression of VEGF-C and VEGFR3,it may play a crucial roles in tumor progression and lymph node metastasis in human pancreatic carcinomas with lymphangiogenesis. VEGF-C, VEGFR-3, MVD and LVD may be significant prognostic factors for lymph node metastasis in pancreatic carcinomas. This implies that inhibitors of lymph angiogenesis could become effective therapeutic options similar to classical angiogenesis inhibitors.