Angiopoietin-2 levels in the hepatic vein as a useful predictor of tumor invasiveness and prognosis in human hepatocellular carcinoma.
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.
Kuboki
Satoshi
S
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shimizu
Hiroaki
H
Mitsuhashi
Noboru
N
Kusashio
Kimihiko
K
Kimura
Fumio
F
Yoshidome
Hiroyuki
H
Ohtsuka
Masayuki
M
Kato
Atsushi
A
Yoshitomi
Hideyuki
H
Miyazaki
Masaru
M
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
D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A