Expressions And Significance Of Annexin-A2,E-cadherin And Vimentin In Hepatolithiasis-associated Intrahepatic Cholangiocarcinoma

Objective: To investigate the expressions of Annexin-A2 and the epithelial-mesenchymal transition(EMT)markers E-cadherin and vimentin in hepatolithiasis-associated intrahepatic cholangiocarcinoma and their significance.Methods: 1.The expressions of Annexin-A2,E-cadherin and vimentin in tumor tissues from 46 patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma(tumor group),Chronic inflammatory bile duct tissues from 50 patients with simple hepatolithiasis(inflammatory group)and normal bile duct tissues form 35 patients undergoing surgical resection for hepatic hemangioma or liver injury(normal group)were determined by immunohistochemical staining.The expressions of the three proteins among the groups was compared and their relations with clinicopathologic factors and prognosis of the patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma were analyzed.2.Western blotting was used to detect the expression of three proteins in fresh bile duct specimens from 5 patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma,5 patients with hepatolithiasis and 5 patients with hemangioma.Results: 1.The results of immunohistochemistry The positive expression rates of both Annexin-A2 and vimentin were presented in descending order as tumor group>inflammation group>normal group(69.6% vs.36.0% vs.11.4%;54.3% vs.28.0% vs.8.6%,all P<0.05),the positive expression rates of E-cadherin was presented in descending order as normal group >inflammation group> tumor group(71.4% vs.48.0% vs.21.7%,all P<0.05).In cholangiocarcinoma tissues,there was a positive correlation between the Annexin-A2 and vimentin expression(r=0.627,P<0.05),and negative correlation between the E-cadherin expression and either the Annexin-A2 or vimentin expression(r=-0.682;r=-0.575,both P<0.05).The expressions of Annexin-A2 and vimentin were significantly associated with the degree of tumor differentiation,lymph node metastasis,Perineural invasion and TNM stage,and E-cadherin expression was significantly associated with the degree of tumor differentiation and lymph node metastasis(all P<0.05).Among the patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma,the survival rate in cases with positive Annexin-A2 or vimentin expression was significantly lower than that in their corresponding negative ones,and the survival rate in cases with negative E-cadherin expression was significantly lower than that in those with its positive expression(all P<0.05).2.The results of western blotting The expression of both Annexin-A2 and vimentin were presented in descending order as tumor group>inflammation group>normal group(all P<0.05);the expression of E-cadherin was presented in descending order as normal group >inflammation group> tumor group(all P<0.05).Conclusions: 1.both Annexin-A2 and vimentin were overexpression,and the expression of E-cadherin was absent or decreasing in the hepatolithiasis-associated intrahepatic cholangiocarcinoma.2.The expression of Annexin-A2,E-cadherin and vimentin is related to invasion and metastasis of hepatolithiasisassociated intrahepatic cholangiocarcinoma.3.There was a positive association between Annexin-A2 overexpression and prognosis(r=-0.682,P< 0.05)and between vimentin overexpression and prognosis(r=-0.575,P< 0.05),but a reverse association between loss of E-cadherin expression and prognosis was observed in patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma.4.Abnormal expression of Annexin-A2,E-cadherin and vimentin play a synergistic role in the development,invasion and metastasis of hepatolithiasis-associated intrahepatic cholangiocarcinoma.5.The Annexin-A2/EMT pathway may probably play an important role in the development and progression of hepatolithiasis-associated intrahepatic cholangiocarcinoma.