Expression And Clinical Significance Of EphB2 In Human Cholangiocarcinoma

Introduction and ObjectiveThe cholangiocarcinoma or cholangiocellular carcinoma is a malignant tumor derived from the epithelium of bile duct.Because of its special anatomical position and characteristic of tending to infiltrate surrounding tissues,vessels and nerves,it is very difficult for radical resection and the prognosis is bad.Documents show that the incidence rate and fatality rate is tending to rise year by year,which is connected with lack of means of early cholangiocarcinoma diagnosis and deep understanding of its pathogenesis.So it is very significant for improving the diagnosis and treatment of cholangiocarcinoma to study deeply its pathogenesis and molecular biological features of metastasis and explore new effective therapeutic methods.Erythropoietin producing hepatocellular(Eph) and its ligand Ephrin is one of the tyrosine kinase receptors families.It is a new angiogenesis factor.The effect of the EphB2 receptors in angiogenesis especially draws concern.It has been verified that the expression of EphB2 in all kinds of tumor tissue is many times higher than that in relevent normal tissue.Although EphB2 is closely connected with the occurrence and progression of many tumors,its relation with cholangiocarcinoma has rarely been studied.Study of the relationship of EphB2 with cholangiocarcinoma will contribute to know the malignant progression mechanism of cholangiocarcinoma and provide a new pathway for cholangiocarcinoma diagnosis and treatment.This experiment analyze the cholangiocarcinoma tissues and normal bile duct tissues to detect the expression of EphB2 protein in every specimen by immunohistochemistry method,analyze the relationship between it and microvessel density and discuss the effect of EphB2 protein in cholangiocarcinoma occurrence and progression and the relationship between it and angiogenesis. MethodsIn this study 28 cholangiocarcinoma specimen by surgecal management from the pathology department of the first affiliated hospital of China Medical University between january 1999 and december 2006 are selected.All specimen are proved by pathology:12 well differentiated adenocarcinoma,9 moderately differentiated adenocarcinoma,7 poorly differentiated adenocarcinoma,in which 7 having lymphnode metastasis and 21 having no lymphnode metastasis.The benign bile duct tissues specimen are from 7 benign cases,in which there are no tumor cells pathologically proved.The expression of EphB2 and CD34 in the cholangiocarcinoma tissues and benign bile duct tissues specimen are detected by by immunohistochemistry method.Statistic analysis was completed with statistic software SPSS12.0,in which homogeneity test of variance and t test were used between two groups comparison and analysis of variance(New-man-keuls method,q test) between three groups or more. Pearson correlation test was used when comparison between the relationship of the expression of EphB2 with MVD.It was considerd that the difference had statistical significance when P<0.05.ResultsEphB2 positive staining was mainly located in cytoplasm or cell membrane with yellowish-brown color.The positive rate of EphB2 expression is 64.29%(18/28),with score 3.11±1.595 in cholangiocarcinoma tissue and 28.57%(2/7),with score 1.571±1.618 in normal tissue and the difference has statistical significance(P<0.01).The difference among every pathological grade groups has no statistical significance(P>0.05).The exepression of EphB2 in the group with lymphnode metastasis is higher than that without lymphnode metastasis with significant statistical significance(P<0.05).The expression of MVD in cholangiocarcinoma tissue is obviously higher than that in corresponding normal bile duct tissue(P<0.05) and they have positive correlation by Pearson correlation statistical treatment.ConclusionEphB2 expression in cholangiocarcinoma tissue is obviously higher than that in normal tissue,which shows EphB2 is related to the occurrence and progression of cholangiocarcinoma.EphB2 expression in cholangiocarcinoma tissue with lymphnode metastasis is obviously higher than that without lymphnode metastasis,which indicates that EphB2 may participate in cholangiocarcinoma metastasis.EphB2 expression in cholangiocarcinoma has positive correlation with microvessel density of cholangiocarcinoma,which indicates that EphB2 may have promoter action in angiogenesis in occurrence and progression of cholangiocarcinoma.