title: ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial-mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins.
  
  
  METHODS
  We immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated.
  
  
  RESULTS
  ZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan-Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival.
  
  
  CONCLUSIONS
  ZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC.
authors.affiliation: Departments of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Terashita
authors.affiliation: Departments of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Chuma
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Hatanaka
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mitsuhashi
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yokoo
authors.affiliation: Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Ohmura
authors.affiliation: Department of Surgery, Sapporo-Kosei General Hospital, Sapporo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishizu
authors.affiliation: Department of Pathology, Sapporo-Kosei General Hospital, Sapporo, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Muraoka
authors.affiliation: Department of Gastroenterology, Sapporo Municipal Hospital, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagasaka
authors.affiliation: Department of Pathology, Sapporo Municipal Hospital, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Hakodate Municipal Hospital, Hakodate, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kurauchi
authors.affiliation: Department of Pathology, Hakodate Municipal Hospital, Hakodate, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Shimoyama
authors.affiliation: Departments of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.affiliation: Departments of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneoka
authors.affiliation: Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Departments of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Departments of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Natsuizaka
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamachi
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kakisaka
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kamiyama
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.affiliation: Departments of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D014746:Vimentin / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism*
chemical_list: D015820:Cadherins; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: CHOLANGIOCARCINOMA; IMMUNOHISTOCHEMISTRY; LIVER CANCER