title: Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor-1 alpha.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a hypervascular tumor and angiogenesis plays an important role in its progression. Angiogenesis is regulated by a balance between pro and antiangiogenic molecules. The aim of this study was to investigate the expressions of angiogenic factors and elucidate their roles in angiogenesis in HCC.
  
  
  METHODS
  We investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), hypoxia-induced factor-1alpha (HIF-1alpha) and thrombospondin-1 (TSP-1) in 60 specimens of surgically resected HCC. We investigated the relationship between their expressions and clinicopathological factors or prognosis.
  
  
  RESULTS
  Ang-2 staining had a significant correlation with the grade of differentiation of HCC cells (P=0.0082). VEGF and Ang-2 expression correlated positively with microvessel density (MVD) (P=0.0061 and 0.0374, respectively). MVD of well-differentiated HCC were significantly lower than those of moderately and poorly differentiated HCC. The disease-free survival time of patients with high Ang-2 and/or HIF-1alpha expression was significantly shorter than that of the low expression group (P=0.0278 and 0.0374, respectively).
  
  
  CONCLUSIONS
  Our study showed that the expression of VEGF and Ang-2 correlated with MVD. Strong Ang-2 expression and/or high nuclear expression of HIF-1alpha is a significant predictive factor for recurrence after curative resection in HCC patients.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yubo
authors.initials: Y
authors.lastname: Yang
authors.forename: Motoi
authors.initials: M
authors.lastname: Kondo
authors.forename: Hideo
authors.initials: H
authors.lastname: Ota
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kato
authors.forename: Bazarragchaa
authors.initials: B
authors.lastname: Damdinsuren
authors.forename: Di
authors.initials: D
authors.lastname: Tang
authors.forename: Sigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.forename: Masato
authors.initials: M
authors.lastname: Sakon
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Kenichi
authors.initials: K
authors.lastname: Wakasa
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A