title: Claudin-18 in biliary neoplasms. Its significance in the classification of intrahepatic cholangiocarcinoma.
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.
authors: Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ashinozaki-tky@umin.ac.jp
authors: Aya
authors: A
authors: Shinozaki
authors: Junji
authors: J
authors: Shibahara
authors: Naohiro
authors: N
authors: Noda
authors: Mariko
authors: M
authors: Tanaka
authors: Taku
authors: T
authors: Aoki
authors: Norihiro
authors: N
authors: Kokudo
authors: Masashi
authors: M
authors: Fukayama
references: Anticancer Res. 2010 Jul;30(7):2995-3003
references: 20683045
references: FEBS Lett. 2011 Feb 18;585(4):606-12
references: 21276448
references: Mod Pathol. 2006 Mar;19(3):460-9
references: 16439986
references: World J Hepatol. 2010 Dec 27;2(12):419-27
references: 21191517
references: Mod Pathol. 2007 Jun;20(6):701-9
references: 17431410
references: Am J Surg Pathol. 2008 Aug;32(8):1182-9
references: 18580680
references: Virchows Arch. 2007 May;450(5):549-57
references: 17429687
references: Histopathology. 2007 Sep;51(3):390-400
references: 17553067
references: Am J Surg Pathol. 2008 Feb;32(2):188-96
references: 18223320
references: Gastroenterology. 2002 Oct;123(4):1052-60
references: 12360467
references: J Cell Biol. 2000 Apr 3;149(1):13-6
references: 10747082
references: Histopathology. 2006 Jul;49(1):35-44
references: 16842244
references: Pathol Int. 2010 Jun;60(6):419-29
references: 20518896
references: J Histochem Cytochem. 2009 Aug;57(8):775-85
references: 19398608
references: BMC Cancer. 2006 Jul 12;6:186
references: 16836752
references: J Histochem Cytochem. 2009 Feb;57(2):113-21
references: 18854598
references: Am J Surg Pathol. 2009 May;33(5):768-74
references: 19194274
references: Am J Surg Pathol. 2007 Jul;31(7):1059-67
references: 17592273
references: J Pathol. 2006 Apr;208(5):633-42
references: 16435283