title: Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression.
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 (<or=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.
authors.affiliation: Department of Pathology, Hamanomachi Hospital, Fukuoka 810-8539, Japan. aishima-s@hamanomachi.jp
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Yunosuke
authors.initials: Y
authors.lastname: Nishihara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Taguchi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Iguchi
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051398:Aquaporin 1 / Q000096:biosynthesis*; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis; D011379:Prognosis
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D051398:Aquaporin 1