目的：探讨高迁移率族蛋白1（HMGB1）和NF-κB 在肝内胆管结石相关肝内胆管癌组织中的表达及其临床意义。方法：用免疫组化法检测40 例肝内胆管结石相关肝内胆管癌组织（肿瘤组）和40 例单纯肝内胆管结石慢性炎症胆管组织（炎症组）及30 例正常胆管组织（正常组）中HMGB1 与NF-κB 的表达，比较各组两种蛋白表达的差异，并分析两种蛋白的表达与肝内胆管结石相关胆管癌患者临床病理特征和预后的关系。结果：HMGB1 与NF-κB 在各组织中的表达强度差异均有统计学意义，两者均表现为肿瘤组> 炎症组> 正常组（均P<0.05）；HMGB1 及NF-κB 在胆管癌组织中的表达呈正相关（χ2=13.713，r=0.586，P<0.05）。HMGB1 的表达与肝内胆管结石相关胆管癌患者肿瘤的分化程度、肿瘤浸润深度、淋巴结转移有关（均P<0.05），而NF-κB 的表达与各因素均无明显关系（均P>0.05）。肝内胆管结石相关肝内胆管癌患者中，HMGB1 阳性者其生存率低于HMGB1 阴性者（P<0.05），而NF-κB 表达与患者生存率无关（P>0.05）。结论：HMGB1/NF-κB 通路可能参与了肝内胆管结石相关肝内胆管癌的发生与发展，其中HMGB1 的表达与肿瘤的恶性程度和患者的预后密切相关。
Expressions and significance of HMGB1 and NF-κB in hepatolithiasis-associated intrahepatic cholangiocarcinoma
Objective: To investigate the expressions and clinical significance of high mobility group protein box l (HMGBl) and NF-κB in tissues of hepatolithiasis-associated intrahepatic cholangiocarcinoma. Methods: The expressions of HMGB1 and NF-κB in tumor tissues from 40 cases of hepatolithiasis- associated intrahepatic cholangiocarcinoma (tumor group), inflammatory bile duct tissues from 40 cases of simple hepatolithiasis (inflammatory group) and normal bile duct tissues form 30 cases undergoing surgical resection for hepatic hemangioma or liver injury (normal group) were determined by immunohistochemical staining. The difference in expressions of the two proteins among the tissues was compared and their relations with clinicopathologic factors and prognosis of the patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma were analyzed. Results: Both expression intensities of HMGB1 and NF-κB among the different tissues were statistically different, which were increased in the order of normal group, inflammatory group, and tumor group,respectively (all P<0.05); there was a positive correlation between the expressions of HMGB1 and NF-κB in cholangiocarcinoma tissue (χ2=13.713, r=0.586, P<0.05). The HMGB1 expression was significantly associated with the degree of tumor differentiation, the depth of tumor invasion and the lymph node metastasis in patients with hepatolithiasisassociated intrahepatic cholangiocarcinoma (all P<0.05), while the NF-κB expression showed no significant relation with any of the selected factors (all P>0.05). In patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma, the survival rate in cases with positive HMGB1 expression was significantly lower than those with negative HMGB1 expression (P<0.05), however, the NF-κB expression exerted no impact on survival (P>0.05). Conclusion: The HMGB1/NF-κB pathway probably participate in the process of occurrence and development of hepatolithiasis-associated intrahepatic cholangiocarcinoma, and HMGB1 expression may exert a decisive impact on degree of malignancy of the tumor and prognosis of the patients.