肝外胆管癌中aPKC-ι、E-cadherin的表达及与侵袭性和预后的关系

目的 研究aPKC-ι和E-cadherin在肝外胆管癌中的表达与临床病理及预后的关系,探讨肝外胆管癌侵袭转移的分子机制.方法 采用免疫组化EnVision法检测9例良性胆管组织、35例肝外胆管癌及6例胆管源性转移癌中aPKC-ι和E-cadherin表达,分析两者与肝外胆管癌临床病理特征、预后及侵袭性的关系.应用Kaplan-Meier法计算累计生存率行单因素预后分析,并经Log-rank检验;选择可能对肝外胆管癌病人预后产生影响的临床及生物学因素进行量化,依次引入COX风险比例模型行多因素回归分析.结果 在肝外胆管癌中,aPKC-ι阳性表达强度明显高于良性胆管组织,E-cadherin阳性表达强度明显弱于良性胆管组织;aPKC-ι表达与肝外胆管癌组织分化程度、侵袭性呈正相关,而E-cadherin表达呈负相关,aPKC-ι与E-cadherin的表达经等级相关分析呈显著负相关(r=-0.387,P＜0.05);单因素生存分析显示aPKC-ι高表达组的肝外胆管癌病人总生存率明显低于低表达组(P＜0.01);多因素回归分析证实aPKC-ι和E-cadherin的表达是影响肝外胆管癌病人预后的独立因素.结论 aPKC-ι和E-cadherin的表达与肝外胆管癌分化程度和侵袭性有关,aPKC-ι和E-cadherin可作为独立的预后判断因子,结合临床病理因素能提高对肝外胆管癌病人预后判断的准确性,aPKC-ι作为一种极化调节相关蛋白在肝外胆管癌侵袭、转移中发挥重要作用.

Correlation of aPKC-ι and E-cadherin expression with invasion and prognosis of extrahepatic cholangiocarcinoma

Objective To investigate the correlation of aPKC-ιand E-cadherin expression with clinicopathological characteristics and prognosis in extrahepatic cholangiocarcinoma and analyze molecular mechanisms of invasion and metastasis in extrahepatie cholangiocarcinoma.Methods EnVision immunohistochemistry was applied to defect the expression of aPKC-ι and E-cadherin in 9 specimens of benign bile duct tissues,35 of extrahepatic cholangiocarcinoma and 6 of metastatic carcinoma of cholangiocarcinoma.The relation of the expression to clinicopathological characteristics,invasion and prognosis of extrahepatic cholangiocarcinoma was analyzed.A multivariate regression analysis was performed in these patients by the computer's Cox proportional hazard model.Results The positive expression intensity of aPKC-ι in extrahepatic cholangiocarcinoma was remarkably stronger than that in benign bile duct tissues,while the expression intensity of E-cadherin was weaker in extrahepatic cholangiocarcinoma than that in benign bile duct tissues.Correlation analysis revealed that the expression of aPKC-ι was positively related to the progress of the tumor pathological differentiation and invasion,whereas that of E-cadherin was entirely contrary.Moreover,there was a negative relationship between the expression of aPKC-ι and that of E-cadherin(r=-0.387,P＜0.05).The univariate analysis showed that all survival rates of the group with higher aPKC-ι expression in extrahepatic cholangiocarcinoma was remarkably less than that in the group with lower expression(P＜0.01).Multivariate analysis revealed that the expression of aPKC-ι and E-cadherin was the most important prognostic factor for extrahepatic cholangiocarcinoma(P＜0.05).Conclusion The expression of aPKC-ιand Ecadherin may reflect the differentiation and invasive potential of extrahepatic cholangiocarcinoma tissues to varying degrees.aPKC-ιand E-cadherin may be independent prognostic factors and,when used in combination with chnicopathological characteristics,may increase accuracy of predicting prognosis of patients with extrahepatic cholangiocarcinoma.As a polar regulative associated protein,aPKC-ιmay play an important role in the invasion and metastasis of extrahepatic cholangiocarcinoma.