Virchows Archiv

, Volume 459, Issue 1, pp 73–80

Claudin-18 in biliary neoplasms. Its significance in the classification of intrahepatic cholangiocarcinoma

  • Aya Shinozaki
  • Junji Shibahara
  • Naohiro Noda
  • Mariko Tanaka
  • Taku Aoki
  • Norihiro Kokudo
  • Masashi Fukayama
Original Article

DOI: 10.1007/s00428-011-1092-z

Cite this article as:
Shinozaki, A., Shibahara, J., Noda, N. et al. Virchows Arch (2011) 459: 73. doi:10.1007/s00428-011-1092-z
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Abstract

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.

Keywords

Claudin-18 Intrahepatic cholangiocarcinoma Intraductal papillary neoplasm of the bile duct Extrahepatic bile duct carcinoma Biliary intraepithelial neoplasia 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Aya Shinozaki
    • 1
  • Junji Shibahara
    • 1
  • Naohiro Noda
    • 1
  • Mariko Tanaka
    • 1
  • Taku Aoki
    • 2
  • Norihiro Kokudo
    • 2
  • Masashi Fukayama
    • 1
  1. 1.Department of Pathology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of MedicineThe University of TokyoTokyoJapan

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