Study On The Expression Of Endostatin And CD31 In Cholangiocarcinoma And Clinical Significance

ObjectsThe engineering endostain can inhibit tumor growth completely and decreaseturnor metastasis in animals. Angiogenesis, the formation of new capillaries from thepreexisting blood vessels, is essential for growth and persistence of tumor beyond a fewmillimeters in size and their metastases. The target of antiangiogenic cancer treatmentis the genetically normal endothelial cell, therefore, the development of resistance toangiostatic therapy is very unlikely, so inhibiting tumor angiogenesis is a promisingnew strategy for treating cancer. About tumor antiangiogenic inhibitors have beenreported, of which endostatin, a newly found potent endogenous inhibitor ofangiogenesis, has the best effect on tumor angiogenesis. Recently, great attention hasbeen paid on the elation between angiogencsis and the pathogenesis, development ofthe tumor. Not only the new blood vessels bring nutrition to the tumors, but they alsogive the tumor cells to be transferred. A great deal of study shows that there is a highrelationship between angiogenesis and tumors metastasis. The microressel density(MVD) of the tumor tissues not only reflect the growth of the tumor blood vesselsquantitatively, but can also predict the progress, metastasis and recurring of thetumour.CD31 are often used to be the markers of MVD. In this study, we detected theexpression of endostatin and CD31 in cholangiocarcinoma tissue byimmunohistochemisty method, and analyzing their correlation, then discussing theirroles in the pathogenesis, development, invasion and metastasis in cholangiocarcinomato provide the new ideas and theory basic for diagnosis, therapy and prevention.Methods1. Materials: Forty-five cholangiocarcinoma patients for operation during 1999 and 2006 were selected, 18 of which were men and 27 were women. They agedfrom 18 to 76. All patients didn't have radiotherapy and chemotherapy before operation.All the resected samples were pathologically detected to determine differentiation,histological type, and tumor staging.2. Methods: Endostatin was detected by immunohistochemistry method in 45cases of cholangiocarcinoma tissue and 11 cases of adjacent normal tissue. Andimmunohistochemistry was used in the MVD calculation by vascular endothelial cellspecific antigen CD31, too. The relationship of endostatin expression and MVD withthe tissue invasion, lymphatic metastasis and prognosis of cholangiocarcinoma wasanalysed retrospectively.Immunohistochemistry: Samples were put into 3% H₂O₂, and antigens wererepaired in microwave oven by 10 minutes in 95-96℃. All samples were blocked in10% goat serum for 30 minutes. First and secondary antibody was put onto the slicesconsecutively, and then SABC and DAB were put on them for color display. Standard:the ration of positive cells0～2score,(-)3～4score (+), 5～8score (++) 9～12score(+++), (+)and up were considered as positive.Results1. Expression of endostatin in different tissues: Of all the 45 patients, the positiveof ES was 71.1% (32/45) in cancer tissues, and 27.3% (3/11) in normal tissues,respectively. The expression of them in cholangiocarcinoma tissues were more than thatin normal tissues (P＜0.05)(See Table 1.).2. There was a close relationship between the expression level of endostatin andwhether there was lymph node metastasis and the position of tumor invasion (P＜0.05).3. MVD was significantly higher in the cancer group (34.88±11.41) than that innormal group (15.80±5.14, P＜0.05)(See Table 3.).4. MVD counting value in low differentiated cholangiocarcinoma was higher thanthat of high differentiated cholangiocarcinoma patients, P＜0.05. MVD counting valuein patients with tissue infiltration of hilus hepatic and lymph node metastasis was higher than that in patients without tissue infiltration of inferior segment of bilecommen duct and no lymph node metastasis, P＜0.05.Conclusion1. Endostatin (ES) is highly expressed in cholangiocarcinorna tissues, andexpression of ES is correlated with lymph node metastasis and position of tumor. ESplays an important role in development of cholangiocarcinoma. 2. CD31 was highlyexpressed in cholangiocarcinoma tissues, and expression of CD31 is correlated withlymph node metastasis, differentiated degree of tumor and position of tumor. 3.Endostatin has close relationship with the angiogenesis of the cholangiocarcinoma, andmay contribute to the restraint of tumor invasion as well as metastasis incholangiocarcinoma. ES expression and MVD value are markers for the invasion,metastasis and prognosis of cholangiocarcinoma.