Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression

Shinichi Aishima, Yousuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Tomohiro Iguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

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30 Citations (Scopus)

Abstract

Aquaporin-1 (AQP-1) has been found to be important in bile formation across cell membranes of the biliary epithelium, and thus it has been suggested that AQP-1 is involved in the pathogenesis of hepatobiliary disease. To clarify the role of AQP-1 in the development of intrahepatic cholangiocarcinoma, we determined AQP-1 expression in the normal bile duct, 21 cases of biliary dysplasia, and in 112 cases of intrahepatic cholangiocarcinoma by immunohistochemical analysis. Mucus core protein 5AC expression, a poor prognostic marker of intrahepatic cholangiocarcinoma, was also assessed in intrahepatic cholangiocarcinoma cases. High (>50%) expression of AQP-1 was detected in 16% (9/58) of the normal large bile ducts examined, and in 48% (10/21) of the biliary dysplasia samples originating from large bile ducts. High (>50%), low (≤50%), and negative AQP-1 expression was observed in 46 (41%), 20 (19%), and 46 (41%) cases of intrahepatic cholangiocarcinoma, respectively. Large tumor size (>40 mm) and poorly differentiated histology were significantly more prevalent in the negative AQP-1 group than in the high AQP-1 group. Low or negative AQP-1 expression was associated with positive lymph node metastasis (P = .0001). AQP-1 expression was found to inversely correlate with that of mucus core protein 5AC, and their distributions tended to be complementary. The low and negative AQP-1 expression was an independent prognostic factor by multivariate survival analysis. We concluded that AQP-1 is up-regulated in biliary dysplasia, as compared with in the normal large bile duct, and down-regulation of AQP-1 is associated with mucin production and aggressive progression of intrahepatic cholangiocarcinoma.

Original languageEnglish
Pages (from-to)1819-1825
Number of pages7
JournalHuman Pathology
Volume38
Issue number12
DOIs
Publication statusPublished - Dec 2007

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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    Aishima, S., Kuroda, Y., Nishihara, Y., Taguchi, K., Iguchi, T., Taketomi, A., Maehara, Y., & Tsuneyoshi, M. (2007). Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression. Human Pathology, 38(12), 1819-1825. https://doi.org/10.1016/j.humpath.2007.04.016