title: Role of histone deacetylase expression in intrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Histone deacetylase (HDAC) plays an important role in chromatin remodeling and gene expression, and in regulating cell cycle progression and differentiation. Furthermore, hypoxic conditions in the malignant tumor enhance HDAC function and increased HDAC activity is closely involved in worse malignant behavior through hypoxia inducible factor (HIF) activation. The aim of this study was to elucidate the correlation between HDAC expression and tumor malignant behavior including HIF-1α expression in intrahepatic cholangiocarcinoma (IHCC).
  
  
  METHODS
  Thirty-five patients with IHCC who underwent hepatic resection were evaluated. HDAC1 and HIF-1α expressions were determined immunohistochemically, and the patients were divided into 2 groups: the HDAC1 positive group (n = 21) and the HDAC1 negative group (n = 14). Clinicopathologic variables including HIF-1α expression were compared between the 2 groups.
  
  
  RESULTS
  HDAC1 expression correlated significantly with higher stage carcinoma, lymph node metastasis, and vascular invasion. The prognosis in the HDAC1 positive group was poorer than in the HDAC1 negative group (5-year survival: 78% vs 8%, P = .001). Furthermore, disease free survival rate in the HDAC1 positive group had significantly worse than that in the HDAC1 negative group (P = .0003). In the multivariate analysis, HDAC1 positive expression was identified as the only independent prognostic factor for disease free survival (Hazard Ratio: 7.194, P = .0018). Furthermore, there was a significant correlation between HDAC1 expression and HIF-1α expression (P = .007).
  
  
  CONCLUSIONS
  These findings suggested that HDAC1 positive expression was a potential new prognostic indicator of IHCC, and a possible promising molecular target through the regulation of HIF-1α.
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. ymorine@clin.med.tokushima-u.ac.jp
authors: Yuji
authors: Y
authors: Morine
authors: Mitsuo
authors: M
authors: Shimada
authors: Shuichi
authors: S
authors: Iwahashi
authors: Tohru
authors: T
authors: Utsunomiya
authors: Satoru
authors: S
authors: Imura
authors: Tetsuya
authors: T
authors: Ikemoto
authors: Hiroki
authors: H
authors: Mori
authors: Jun
authors: J
authors: Hanaoka
authors: Hidenori
authors: H
authors: Miyake
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1