Different roles of inducible nitric oxide synthase and cyclooxygenase-2 in carcinogenesis and metastasis of intrahepatic cholangiocarcinoma
Different roles of inducible nitric oxide synthase and cyclooxygenase-2 in carcinogenesis and metastasis of intrahepatic cholangiocarcinoma
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DOI：
10.1016/j.humpath.2012.09.004
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发表时间：
2013-06-01
期刊：
影响因子：
3.3
通讯作者：
Oda, Yoshinao
中科院分区：
文献类型：
--
作者：
Aishima, Shinichi;Mono, Yohei;Oda, Yoshinao
诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）与慢性炎症和肿瘤发生有关。然而，关于iNOS和考克斯-2在胆管癌及其前病变和转移灶中的生物学意义，目前还知之甚少。我们检测了40例胆管上皮内瘤变、134例原发性肝内胆管细胞癌和27例转移淋巴结组织中iNOS和考克斯-2的表达，并分析其与胆管上皮内瘤变分级、临床病理因素和预后的关系。iNOS和考克斯-2在反应性上皮和胆管上皮内瘤变中呈高表达。在肝内胆管癌中，淋巴管浸润和淋巴结转移与iNOS阴性表达（分别为P = 0.0002，P = 0.0324）和考克斯-2阳性表达（分别为P = 0.0012，P = 0.0063）显著相关。血管内皮生长因子-C表达与考克斯-2表达相关（P = 0.0053），但与iNOS表达无关。原发性肝内胆管癌中考克斯-2的表达高于转移性淋巴结（P < .0001）。考克斯-2阳性表达提示肝内胆管细胞癌预后差（P = 0.0273）。本研究提示iNOS和考克斯-2可能通过胆管上皮内瘤变参与了胆管癌的发生，但在肝内胆管癌的转移过程中起着不同的作用。考克斯-2可能通过血管内皮生长因子-C途径参与了较高的淋巴管浸润和转移。(C)2013 Elsevier Inc. All rights reserved.
Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been implicated in chronic inflammatory conditions and carcinogenesis. However, little is known about the biological significance of iNOS and COX-2 in cholangiocarcinoma or its precursors or metastatic lesions. We examined iNOS and COX-2 immunohisotochemical expression in 40 biliary intraepithelial neoplasias, 134 primary intrahepatic cholangiocarcinoma cases, and 27 metastatic lymph nodes and analyzed the correlations with grade of atypia of biliary intraepithelial neoplasia, clinicopathological factors and outcomes of intrahepatic cholangiocarcinoma. iNOS and COX-2 expression was highly expressed in reactive epithelium and biliary intraepithelial neoplasia. In intrahepatic cholangiocarcinoma, lymphatic invasion and lymph node metastasis were significantly correlated with negative iNOS expression (P = .0002, P = .0324, respectively) and positive COX-2 expression (P = .0012, P = .0063, respectively). Vascular endothelial growth factor-C expression was associated with COX-2 expression (P = .0053), but not with iNOS expression. COX-2 expression in primary intrahepatic cholangiocarcinoma was higher than that in metastatic lymph nodes (P < .0001). COX-2-positive expression indicated a poor intrahepatic cholangiocarcinoma outcome (P = .0273). This study indicates that iNOS and COX-2 may play roles in carcinogenesis via biliary intraepithelial neoplasia, but play different roles in metastasis of intrahepatic cholangiocarcinoma. COX-2 may participate in a higher lymphatic invasion and metastasis via the vascular endothelial growth factor-C pathway. (C) 2013 Elsevier Inc. All rights reserved.