title: Angiopoietin-2 levels in the hepatic vein as a useful predictor of tumor invasiveness and prognosis in human hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is characteristically a hypervascular tumor and its progression is known to be closely related to angiogenesis. In this study, we investigated angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) levels in the hepatic vein draining from HCC, as well as in the peripheral vein, to evaluate their relation to clinicopathological features and prognosis.
  
  
  METHODS
  To obtain hepatic venous blood samples, a catheter was placed into the main branch of the hepatic vein draining from HCC in 21 patients. The Ang-2 and VEGF levels in both the hepatic and peripheral veins were investigated. Furthermore, Ang-2 mRNA expression in surgically resected HCC was evaluated by quantitative reverse-transcription polymerase chain reaction (RT-PCR), as well as microvessel density (MVD) by CD34 immunostaining.
  
  
  RESULTS
  Ang-2 levels in the hepatic vein significantly correlated with Ang-2 mRNA expression in HCC, but Ang-2 levels in the peripheral vein did not correlate. Furthermore, a significant correlation was found between hepatic venous Ang-2 and MVD levels, whereas there was no significant correlation with hepatic venous VEGF levels. When hepatic venous Ang-2 levels were compared with clinicopathological features, a significant relationship was found between high Ang-2 levels and portal vein invasion. The survival for patients in the high hepatic venous Ang-2 group was significantly poorer when compared with the low group.
  
  
  CONCLUSIONS
  Preoperative hepatic venous Ang-2 levels may be a good predictor for portal vein invasion and also prognosis in patients with HCC.
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuboki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Noboru
authors.initials: N
authors.lastname: Mitsuhashi
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kusashio
authors.forename: Fumio
authors.initials: F
authors.lastname: Kimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshidome
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshitomi
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy; D006503:Hepatic Veins / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008833:Microcirculation / Q000737:chemistry / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A