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目的:探讨膜联蛋白A2(annexin A2)与上皮-间质转化(EMT)标志物上皮细胞钙黏蛋白(E-cadherin)及波形蛋白(vimentin)在肝内胆管结石相关肝内胆管癌中的表达及意义。方法:用免疫组化检测46例肝内胆管结石相关肝内胆管癌组织(肿瘤组)、50例单纯肝内胆管结石慢性炎症胆管组织(炎症组)及35例来自血管瘤旁和肝外伤的正常胆管组织(正常组)中annexin A2、E-cadherin、vimentin的表达,比较各组3种蛋白表达的差异,并分析3种蛋白的表达与肿瘤组患者临床病理特征及预后的关系。结果:annexin A2与vimentin的阳性表达率在肿瘤组、炎症组、正常组均呈依次明显降低(69.6%vs.36.0%vs.11.4%;54.3%vs.28.0%vs.8.6%,均P<0.05),而E-cadherin的阳性表达率则相反(21.7%vs.48.0%vs.71.4%,均P<0.05);在胆管癌组织中,annexin A2与vimentin的表达呈正相关(r=0.627,P<0.05),E-cadherin的表达与annexin A2、vimentin的表达均呈负相关(r=-0.682;r=-0.575,均P<0.05)。annexin A2、vimentin的表达与肿瘤的分化程度、淋巴结转移、TNM分期有关,E-cadherin的表达与肿瘤的分化程度、淋巴结转移有关(均P<0.05)。肝内胆管结石相关肝内胆管癌患者中,annexin A2和vimentin各自阳性者的生存率低于其各自阴性者,E-cadherin阴性者生存率低于其阳性者(均P<0.05)。结论:annexin A2/EMT通路在肝内胆管结石相关肝内胆管癌的发生和发展中可能至关重要,annexin A2、E-cadherin及vimentin的表达与肿瘤的恶性程度和患者预后密切相关。
Objective: To investigate the relationship between annexin A2 and epithelial-mesenchymal transition (EMT) markers E-cadherin and vimentin in intrahepatic cholangiocarcinoma associated intrahepatic cholangiocarcinoma Expression and meaning. Methods: Forty-six cases of intrahepatic cholangiocarcinoma (tumor group), 50 cases of chronic intrahepatic bile duct stones (inflammation group) and 35 cases of hepatolithiasis and hepatic trauma The expressions of annexin A2, E-cadherin and vimentin in normal bile duct tissue (normal group) were compared. The expression of three proteins in each group was compared with the clinicopathological features and prognosis of tumor patients. Results: The positive rates of annexin A2 and vimentin were significantly decreased in the tumor group, inflammatory group and normal group (69.6% vs.36.0% vs.11.4%, 54.3% vs.28.0% vs.8.6%, all P < 0.05), while the positive rate of E-cadherin was the opposite (21.7% vs.48.0% vs.71.4%, all P <0.05). In cholangiocarcinoma, the expression of annexin A2 was positively correlated with vimentin (r = P <0.05). The expression of E-cadherin was negatively correlated with the expression of annexin A2 and vimentin (r = -0.682; r = -0.575, all P <0.05). The expression of annexin A2 and vimentin was correlated with tumor differentiation, lymph node metastasis and TNM staging. The expression of E-cadherin correlated with tumor differentiation and lymph node metastasis (all P <0.05). Among the patients with intrahepatic cholangiocarcinoma associated intrahepatic cholangiocarcinoma, the survival rates of both positive individuals with annexin A2 and vimentin were lower than those with negative ones, while those with negative E-cadherin were lower than those with positive ones (all P <0.05). Conclusions: The annexin A2 / EMT pathway may play an important role in the pathogenesis and development of intrahepatic cholangiocarcinoma associated with intrahepatic bile duct stones. The expression of annexin A2, E-cadherin and vimentin is closely related to the malignancy and prognosis.