Expression Of VEGF-B And Its Receptor Flt-1 In Hepatocellular Carcinoma

Objective: Primary liver cancer is a common digestion system malignant tumor in our country. Its annual mortality is deuto-position in malignant tumors, clinical symptom appears late, many patients are middle or advanced stage when symptoms show up, rate of surgery is low, prognosis is poor Orthodox operation chemotherapy radiotherapy can not obtain satisfactory effect because of theirs locals. The reason is that tumor has powerful growth and metastasis potentia. Growth and metastasis of tumor depend on angiogenesis, the most key factor is vascular endothelial growth factor family (VEGFs) in encouraging angiogenesis. VEGFs include VEGF-A,B,C,D,and PIGF (placenta growth factor). Recently, many studies reveal that VEGF has abnormal expression in many malignant tumors. VEGF-B and its receptor Flt-1 are found in human nervous system tumor, breast carcinoma, renal carcinoma, cancer of colon ,lung cancer etc. They have relation to lymphatic vessel invasion and lymphatic metastasis of colon and lung cancer; Regulate formation of tumor vessel in renal carcinoma; They have correlation with lymphatic metastasis, not promote angiogenesis in breast caicinoma; In process of malignant neurospongi-oma vessel formation, they may play a role as a assistance factor. At present, the therapy with anti-VEGF receptor provides a new method for breast cancer. But, the expression and significance of VEGF-B and its receptor in hepatocellular carcinoma haven't been found in reports. The aim of this study is to evaluate expression of VEGF-B and its receptor Flt-1 in liver cancer, para-tumor and normal liver tissue, and analyze the relationships between the expression and the clinicopathological characteristics of liver cancer .Methods: Fifty-five tumor tissues , 32 tumor-surround- ing tissues were obtained from patiens with liver cancer undergoing surgery, and 15 nomal liver tissue samples were obtained from patiens undergoing surgery. Immunohistochemistry is used to detect expression of VEGF-B and Flt-1. X2 and Log-rank were used to determine the relationship between the expression and clinicopathological parameters of liver cancer.Results1 Expression of VEGF-B and Flt-1 protein in liver cancer, para-tumor and normal liver tissue: VEGF-B-positive stain rate was 76.4% (42/55) in liver cancer tissue, 54.5% (18/33) in para-tumor tissue and 33.3% (5/15) in normal liver tissue; Flt-1-positive stain rate was 72.7% (40/55) in liver cancer tissue, 48.5% (16/33) in para-tumor tissue and 26.7% (4/15) in normal liver tissue. X2 analysis indicuted that VEGF-B-positive stain rate and Flt-1-positive stain rate in liver cancer tissue were significant higher than in para-tumor tissue (P<0.05) and normal liver tissue (P<0.05) . 2 VEGF-B-positive stain rate was 100.0% (11/11) in liver cancer tissue with bile duct or portal vein tumor embolus and was 70.4% (31/44) in without bile duct or portal vein tumor embolus. There was a statistical significant difference between with and without bile duct or portal vein tumor embolus (P<0.05). X2 analysis indicuted that the presence of VEGF-B in the cancer cells was associated with a statistical significant progress in clinical stage, with or without capsual in tumor, metastasis in liver or lymph node(P<0.05); However, there was no significant difference with age, sex, tumor size, tumor differentiation and AFP(P>0.05).3 Flt-1-positive stain rate was 100.0% (11/11) in liver cancer tissue with bile duct or portal vein tumor embolus and was 65.92% (29/44) in that without bile duct or portal vein tumor embolus. There was a significant difference between with and without bile duct or portal vein tumor embolus (P<0.05). X2 analysis indicuted that the presence of Flt-1 in the cancer cells was associated with a statistical significant progress in clinical stage, with or without capsual in tumor, metastasis in liver or lymph node(P<0.05); However, there was no significant difference with age, sex, tumor size, tumor differentiation and AFP(P>0.05).4 Both of VEGF-B-positive and Flt-1-positive stain was observed in 34 of 55 hepatocellular carcinoma tissue samples, VEGF-B-negative and Flt-1-negative stain was observed in 11 of 55 hepatocellular carcinoma tissue samples, There was a significantly difference(P<0.01).5 One-year and 2-year survival rate of 55 patients were 51.28% and 28.84% respectively; One year and 2-year survival rate in patients with VEGF-B-positive were 45.82% and 21.38% respectively, and in patients with VEGF-B-negative stain were 69.93% and 52.40% respectively, Log-rank analysis indicated that there was significant difference between the positive group and the negative group (P<0.05); One-year and 2-year survival rate in patients with Flt-1-positive stain were 45.71% and 15.64% respectively, and in patients with Flt-1-negative stain were 78.32% and 62.66% respectively, Log-rank analysis indicated that there was significant difference between the positive group and the negative group (P<0.05); One-year and 2-year survival rate in patients with bile duct or portal vein tumor embolus were 45.82% and 21.38% respectively, and in patients without bile duct or portal vein tumor embolus were 59.74% and 36.60% respectively, Log-rank analysis indicated that there was significant difference between the patients with and without bile duct or portal vein tumor embolus. (P<0.05).Conclusion1 Expression of VEGF-B and Flt-1 in liver cancer tissue were significantly higher than in para-tumor tissue and normal liver tissue, expression in cancer tissue was the highest; The expression of liver cancer cells was significant associated with clinical stage, with or without capsual, with or without liver or lymph node metastasis, with and without bile duct or portal vein tumor embolus (P<0.05); But it not associated with age, gender, tumor size, tumor differentiation and AFP level(P>0.05).2 There was a significantly correlation between VEGF-B expressions of and Flt-1 expression in liver cancer, it suggested VEGF-B and Flt-1 present relation of ligand-receptor.3 The accumulate survival rate of patients with VEGF-B-positive stain and Flt-1-positive stain was significantly lower than that of patients with VEGF-B-negative stain and Flt-1- negative stain. It suggested that there was a close correlation between VEGF-B expression or Flt-1 expression and patients'prognosis with liver cancer.