Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Virchows Arch. 2011 Jul;459(1):73-80. doi: 10.1007/s00428-011-1092-z. Epub 2011 May 24.
Claudin-18 (CLDN18), a tight junction protein specific to stomach and lung, is aberrantly expressed in preinvasive and invasive neoplasms of the pancreas. To investigate the significance of CLDN18 expression in biliary neoplasms, immunohistochemical analysis was performed. CLDN18 expression was frequently observed in the epithelial cells of extrahepatic bile duct carcinomas (90%, n = 99), intrahepatic intraductal papillary neoplasms of the bile duct (IPNBs, 100%, n = 11), and extrahepatic IPNBs (89%, n = 9), while it was less frequent in intrahepatic cholangiocarcinomas (ICCs, 43%, n = 83). Interestingly, CLDN18 expression was also frequently observed in precancerous lesions such as biliary intraepithelial neoplasias (78%, n = 18). Among ICCs, CLDN18-positive cases showed higher frequencies of periductal infiltrative growth, perineural invasion, and lymph node metastasis. Multivariable analysis demonstrated that positive CLDN18 expression was an independent risk factor for lymph node metastasis in ICCs. Furthermore, CLDN18 expression was associated with poor overall survival by univariable analysis, as well as lymph node metastasis. These results suggest that CLDN18 may play an important role in biliary carcinogenesis, and especially in ICCs, it is associated with aggressive behavior and serves as a useful marker for the classification of ICC.
Claudin-18（CLDN18）是一种特异性表达于胃和肺的紧密连接蛋白，在胰腺的癌前和侵袭性肿瘤中异常表达。为了研究 CLDN18 表达在胆道肿瘤中的意义，进行了免疫组织化学分析。CLDN18 表达在肝外胆管癌（90%，n=99）、肝内胆管内乳头状肿瘤（IPNBs，100%，n=11）和肝外 IPNBs（89%，n=9）的上皮细胞中频繁观察到，而在肝内胆管癌（ICC，43%，n=83）中则较少见。有趣的是，CLDN18 表达也在癌前病变如胆管上皮内肿瘤中频繁观察到（78%，n=18）。在 ICC 中，CLDN18 阳性病例表现出更高的导管周围浸润性生长、神经周围侵犯和淋巴结转移的频率。多变量分析表明，CLDN18 阳性表达是 ICC 淋巴结转移的独立危险因素。此外，CLDN18 表达与单变量分析的总体生存不良以及淋巴结转移相关。这些结果表明 CLDN18 可能在胆道癌发生中发挥重要作用，特别是在 ICC 中，它与侵袭性行为相关，并可作为 ICC 分类的有用标志物。
