title: Hypoxia inducible factor expression in intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  Intrahepatic cholangiocarcinoma (IHCC) is known to be one of the most malignant tumors. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions. The aim of this study was to elucidate the role of HIF-1 in IHCC.
  
  
  METHODS
  Thirty-five patients with IHCC who underwent hepatic resection were enrolled in this study. The expression of HIF-1a was determined immunohistochemically and the patients were divided into two groups: HIF-1a positive group (n=22) and HIF-1a negative group (n=13). Clinicopathological variables including prognosis were compared between the two groups. The prognostic factors were investigated by multivariate analysis using Cox's proportional hazard model.
  
  
  RESULTS
  HIF-1a expression correlated significantly with higher stage, and tended to correlate with tumor diameter (>4cm), vessels infiltration and intrahepatic metastasis. The prognosis in HIF-1a positive group was poorer than that in HIF-1a negative group (5-year survival: 62.9% vs. 18.3%). Furthermore, HIF-1a positive expression was identified as an independent prognostic factor for both overall and disease free survival.
  
  
  CONCLUSIONS
  The findings suggested that the intratumoral HIF-1a regulated malignant behavior and was a new prognostic indicator of IHCC.
authors.affiliation: Department of Surgery, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Jun
authors.initials: J
authors.lastname: Hanaoka
authors.forename: Mami
authors.initials: M
authors.lastname: Kanamoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Miyake
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D015415:Biomarkers / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D051793:Hypoxia-Inducible Factor 1