The Expression Of VEGF,VEGF-C And CK20 Protein In Invasion And Metastasis Of Cholangiocarcinoma

Objective: Cholangiocarcinoma is one of the malignant tumors those are difficult to detect in early stage and has a bad prognosis. The incidence of cholangiocarcinoma in our country is around 0.01%～0.46% and has an increasing tend from year to year. The main reason causes cholangiocarcinoma hard to treat and has a high rate of recurrence after operation is it has a tendency of invasion and metastasis. Recently, more studies found that the generation of blood and lymphatic vessels play an important role in the progression, invasion and prognosis of tumor. The research on the generation of blood and lymphatic vessels of tumor are focused on VEGF family. VEGF (vascular endothelial growth factor) is believed to be one of the most important factors to stimulate the proliferation of vascular endothelial cell. VEGF-C discovered recently is a new member of VEGF family. It is a specific growth factor for lymphatic endothelial cells. It can accelerate the process of angiogenesis and lymphangiogenesis, as well as metastatic spread via the lymphatic system. CK20, a cytoskeleton of cell, is known to express in a variety of malignant tumor. As a maker, it can find applications in many research fields of tumor. In this study, we investigated the expression of VEGF, VEGF-C and CK20 protein in cholangiocarcinoma and normal bile duct tissues, in order to find out the role in the invasion and metastasis of cholangiocarcinoma and try to clarify the mechanism. Furthermore, this study can provide theoretical and experimental foundation to treat malignant tumor and prevent metastasis and recurrence with interrupting the process of angiogenesis and lymphangiogenesis.Methods: In this study we have investigated the expression of VEGF, VEGF-C and CK20 protein in 49 cases of cholangiocarcinoma and 16 cases normal bile duct tissues by immunohistochemistry. The different expression levels in two kinds of specimens were dealed with statistical analysis, so were the correlation between the expression and the clinic pathologic character, as well as the correlation among the three.Results: 1 The expression of VEGF, VEGF-C and CK20 in cholangiocarcinoma and normal bile duct: The percentage of VEGF-positive and VEGF-C-positive expression was 65.3%(32/49) and 69.4%(34/49) in tumor group, which was 25.0%(4/16) and 18.8%(3/16) in normal group. The percentage of the VEGF-positive tissue and VEGF-C-positive tissue was significantly higher in the cholangiocarcinoma than in the normal bile duct (P<0.01). The percentage of CK20-positive expression was 73.5%(36/49) in tumor group, which was 12.5%(2/16) in normal group. The percentage of the CK20-positive tissue was significantly higher in the cholangiocarcinoma than in the normal bile duct (P<0.01). These results showed that the expression levels of VEGF, VEGF-C and CK20 proteins were higher in cholangiocarcinoma than in normal. They had intensive correlation with the growth of cholangiocarcinoma.2 The correlation between the expression of VEGF protein and the clinic pathologic character: This study showed that the expression of VEGF protein in cholangiocarcinoma is significantly related with tumor invasion, differentiation and lymph node metastasis (P<0.01), and not related with patient's age, sex, the size and clinical stage of tumor according to UICC (P>0.05). The percentage of strongly expressed VEGF protein were 88.9%(16/18), 60.9%(14/23) and 25.0%(2/8) in poorly, moderately and well-differentiated adenocarcinoma respectively. Statistical analysis showed difference was significant (P<0.01). The VEGF expression level had negative linear correlation with the degree of histologic differentiation of cholangiocarcinoma (r=-0.439,P=0.002). The positive expression rate of VEGF was 84.0%(21/25) in lymph node metastasis group, which was 45.8%(11/24) in no lymph node metastasis group. Statistical analysis showed difference was significant (P<0.01). The positive expression rate of VEGF was 83.3%(25/30) in the invasion group, which was 36.8%(7/19) in the no-invasion group. Statistical analys...