Expression Of Vascular Endothelial Growth Factor D And It's Receptor Flt-4 In Human Pancreatic Cancer

Objective: The pancreatic cancer is one of the most common malignant tumors in our country, which is characterized by a low resectability rate and a low long-term survival rate. The 1-year survival rate of pancreatic cancer is under 10%, and the 5-year survival rate is only 3%, thus the prognosis is one of the worst among the digestive cancers. Invasion and metastasis is considered as the main reason for the worst prognosis and the vascular endothelial growth factor family (VEGFs) is considered playing an important role in the process of invasion and metastasis. Recently, majority research revealed that the VEGFs have a high expression in varied malignant tumors, and are associated with the invasion, metastasis and prognosis of the tumors. VEGF-D, a member of VEGFs, as the ligand of the fms-like tyrosine kinase-4 (Flt-4), has an important effect on the lymphagiogenesis. The aim of this study is to evaluate the expression of VEGF-D and Flt-4 in pancreatic cancer, para-tumor and normal pancreatic tissue, and analyze the relationships between the expression and the clinicopathological characteristics of pancreatic cancer influencing factors.Methods: Forty-eight tumor tissue samples and thirty-two tumor-surrounding tissue samples were obtained from patients with pancreatic cancer undergoing radical resection, thirteen normal pancreatic tissue samples as the control. Immunohistochemistry was used to detect expression of VEGF-D and Flt-4. Statistical analysis was used to determine the relationship between the expression and clinicopathological parameters of pancreatic cancer.Results: 1 Expression of VEGF-D and Flt-4 protein in pancreatic cancer, para-tumor and normal pancreatic tissue: VEGF-D-positive stain rate was 58.3% (28/48) in pancreatic cancer tissue, 81.3% (26/32) in para-tumor tissue and 23.1% (3/13) in normal pancreatic tissue. Flt-4-positive stain rate was 63.5% (30/48) in pancreatic cancer tissue, 87.5% (28/32) in para-tumor tissue and 30.8% (4/13) in normal pancreatic tissue. Statistical analysis revealed that VEGF-D-positive stain rate and Flt-4-positive stain rate in pancreatic cancer tissue were higher than in normal pancreatic tissue (P<0.05) and lower than in para-tumor tissue (P<0.05).2 Relationship between VEGF-D and Flt-4 protein expressions in pancreatic carcinoma: Both of VEGF-D-positive and Flt-4-positive stain was observed in 26 of 48 pancreatic carcinoma tissue samples, VEGF-D-negative and Flt-4-negative stain was observed in 16 of 48 pancreatic cancer tissue samples. There is a significantly correlation (P<0.01).3 VEGF-D protein expression in relation to the clinicopathological characteristics of 48 patients with pancreatic carcinoma: VEGF-D-positive stain rate was 91.7% (11/12) in pancreatic carcinoma tissue with lymph node metastasis and was 47.2% (17/36) in that without lymph node metastasis. VEGF-D-positive stain rate in patients with lymph node metastasis is higher than in patients without lymph node metastasis(P<0.01), and it is distinctly correlated with clinical stage and encroachment of duodenum(P<0.05), but it did not relate to age, sex, tumor size, encroachment of surrounding soft tissue (P>0.05).4 Flt-4 protein expression in relation to the clinicopathological characteristics of 48 patients with pancreatic carcinoma: Flt-4-positive stain rate was 91.7% (11/12) in pancreatic carcinoma tissue with lymph node metastasis and was 52.8% (19/36) in that without lymph node metastasis. Flt-4-positive stain rate in patients with lymph node metastasis is higher than in patients without lymph node metastasis (P<0.01), and it is distinctly correlated with clinical stage and encroachment of surrounding soft tissue (P<0.05), but it did not relate to age, sex, tumor size, encroachment of duodenum (P>0.05).5 VEGF-D protein, Flt-4 protein and lymph node metastasis in relation to the median survival time of 48 patients with pancreatic carcinoma: The median survival time of 48 patients with pancreatic carcinoma was 12 month. The median survival time was 7 month in patients with VEGF-D-positive and was 16 month in patients with VEGF-D-negative stain. The median survival time was 8 month in patients with Flt-4-positive stain but was 16 month in patients with Flt-4-negative stain. The median survival time was only 5 month in patients with lymph node metastasis and was 14 month in patients without lymph node metastasis. The median survival time of patients with VEGF-D-positive stain, Flt-4-positive stain and with lymph node metastasis was significantly lower than that of patients with VEGF-D-negative stain, Flt-4- negative stain and without lymph node metastasis, respectively (P<0.05).Conclusion: 1 The expression of VEGF-D and Flt-4 in pancreatic cancer tissue were significantly higher than in normal pancreatic tissue and were lower than in para-tumor tissue.2 There was a significantly correlation between the expressions of VEGF-D and Flt-4 in pancreatic cancer, and the expression of VEGF-D and Flt-4 protein may be contribute to pancreatic cancer lymph node metastasis.3 The median survival time of patients with VEGF-D-positive stain and Flt-4-positive stain was significantly lower than that of patients with VEGF-D-negative stain and Flt-4- negative stain.