The Expression Of E-cadherin And N-cadherin In Hepatocellular Carcinoma And Their Correlation And Clinical Significance

Background and aims: This study aims to investigate the expression of N-cadherin andE-cadherin in HCC and analyze the correlation between N-cadherin and E-cadherinexpression and their clinical significance.Methods:86patients with a single HCC smaller than5cm in diameter who underwentcurative liver resection, in the hepatic surgery center of tongji hospital affiliated tongjimedical college of huazhong university of science and technology, between2002and2009were enrolled in this study. N-cadherin and E-cadherin expressions in HCC andadjacent liver tissues were studied by immunohistochemistry and immunofluorescenceassays, the relationship between N-cadherin and E-cadherin expressions of HCC andclinical pathological factors and their correlation was evaluated. Disease-free survival andoverall survival were analyzed by the Kaplan-Meier method, and differences in survivalbetween these groups were compared using the log-rank test. The relationships betweenthe E-and N-cadherin expressions were tested by the Spearman’s rho pairwise bivariatecorrelations testResults:53of86(61.6%) patients were found with reduced E–cadherin expression, and33of86(38.4%) with preserved E-cadherin expression.63of86(73.2%) patients werefound with reduced N-cadherin expression, and23of86(26.8%) patients with preservedN-cadherin expression. The1-and3-year disease-free survival rates and overall survivalrates were35.7%and31%,72.2%and38.3%, respectively, in patients with reducedE-cadherin expression, and84.8%and81.8%,97%and87.9%, respectively, in thepatients with preserved E-cadherin expression. There was a significant difference in1-and3-year disease-free survival rates and overall survival rates between the patients withreduced E-cadherin expression and those with preserved E-cadherin expression（P<0.001）.the1-and3-year disease-free survival rates and overall survival rates were91.3%and87%,100%and91.3%, respectively, in the patients with preserved N-cadherinexpression, and41.8%and38%,75.3%and46%, respectively, in the patients withreduced N-cadherin expression.（P<0.001）. There was a significant difference in1-and 3-year disease-free survival rates and overall survival rates between the patients withreduced N-cadherin expression and those with preserved N-cadherin expression（P<0.001）In23patients with negative expression of E-cadherin in tumors,19tumors were alsoidentified with negative expression of N-cadherin. In30patients with heterogeneousexpression of E-cadherin in tumors,20tumors were identified with heterogeneousexpression of N-cadherin. In33patients with uniformly positive expression of E-cadherinin tumors,19tumors were identified with uniformly positive expression of N-cadherin.Positive correlation was observed between the same expression patterns in bothN-cadherin and E-cadherin expressions (r=0.744). Concurrent loss of both N-cadherinand E-cadherin expression was significantly associated with absence of tumor capsule,vascular invasion and poor differentiation. Moreover, the1-and3-year disease-free andoverall survival rates were27%and18%, and64.3%and14.3%, respectively, in thepatients with concurrent loss of both N-cadherin and E-cadherin expressions, which weresignificantly worse than those with concurrent preserved expressions or heterogeneousexpressions of N-cadherin and E-cadherin (p<0.001).Conclusions: Loss of N-cadherin expression was positively correlated with loss ofE-cadherin in HCC. The concurrent loss of both N-cadherin and E-cadherin expressionswas associated with poor surgical outcomes of HCC patients undergoing liver resection.The prevailing concept of antagonistic roles of these two cadherins in the so-calledepithelial-mesenchymal transition cadherin switch seems need to be reconsidered in HCC.