Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

AIM: To examine the immunoreactivity of E-cadherin and four subtypes of catenin family in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/ catenin complex and clinicopathologic parameters of HCC patients. METHODS: An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. RESULTS: Reduced expression of E-cadherin, α-, β-, γ-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade (P = 0.000). It showed significant difference between expression of catenin members and tumor stage (P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively). The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis (IM) and capsular invasion (P = 0.008, P = 0.03, respectively). A close correlation was also observed between the expression of catenins and the tumor size (P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively). In addition, the expression of each catenin was found correlated with IM (P = 0.012, P = 0.049, P =0.026 and P = 0.014, respectively). No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value (P = 0.035). The expression of E-cadherin was consistent with α-, β-, γ-catenin and p120 expression (P = 0.000). Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients' survival (P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively). Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. CONCLUSION: Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient's survival.

Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters

AIM:To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma(ICC) . METHODS:An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS:The expression of E-cadherin and P120 was reduced in 27 cases(64.3%) and 31 cases(73.8%) ,respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade(χ2 = 9.333,P = 009 and χ2 = 11.71,P = 0.003) ,TNM stage(χ2= 8.627,P = 0.035 and χ2 = 13.123,P = 0.004) ,intrahepatic metastasis(χ2= 7.292,P = 0.007 and χ2 = 4.657,P = 0.041,respectively) and patients' survival(χ2= 6.351,P = 0.002 and χ2 = 4.023,P = 0.000,respectively) . In addition,the expression of P120 was in concordance with that of E-cadherin(χ2 = 13.797,P = 0.000) ,indicating that the expression of P120 may be dependent on that of E-cadherin. Finally,only P120 expression was found to be an independent prognostic factor in Cox regression model(r = 0.088,P = 0.049) . CONCLUSION:Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markersfor predicting tumor invasion,metastasis and patients' survival,but only P120 is an independent prognostic factor for ICC.

Dysregulation of β-catenin by hepatitis B virus X protein inHBV-infected human hepatocellular carcinomas

β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway.In our study,we found that,in the development of hepatocellular carcinoma(HCC),β-catenin was correlated with hepatitis B virus(HBV)X gene encoded protein,which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis.The expression levels of wild-typeβ-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein(HBx),accompanied by destabilization of adherens junction.Reverse transcrip-tase PCR(RT-PCR),Northern and Western blot showed that reduction of wild-typeβ-catenin expression involved degradation of the protein.However,RNA interference(RNAi)and luciferase assay indicated that HBx enhancedβ-catenin mediated signaling in HepG2 cells.In addition,immunohistochemical and Western blot analysis ofβ-catenin revealed that a decrease in theβ-catenin protein level was found in 58.3%of HBV-related HCCs versus 19.2%of non-HBV-related tumors.Our data suggest that the expression of HBx contributed to the development of HCC,in part,by repressing the wild-typeβ-catenin expression and enforcingβ-catenin-dependent signaling pathway,thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.