Serum endostatin predicts tumor vascularity in hepatocellular carcinoma.
BACKGROUND
Tumor angiogenesis is a strong prognostic factor in patients with hepatocellular carcinoma (HCC). However, to the authors' knowledge, details regarding the serum levels of proangiogenic and antiangiogenic growth factors controlling this process are not yet known.


METHODS
Serum endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) levels were measured by the enzyme immunoassay method in prospectively collected samples from 33 HCC patients who had received no preoperative therapy. The angiogenic score (AS) and endostatin localization were evaluated using immunohistochemistry.


RESULTS
Significant decreases in serum endostatin (P = 0.0007) and bFGF (P = 0.0004) were observed in postoperative samples compared with the preoperative values. A very strong direct correlation was noted between VEGF and endostatin (P < 0.0001). Only the preoperative serum endostatin was found to have a significant (P = 0.0025) inverse correlation with the AS. Furthermore, the combined positivity for bFGF and VEGF and negativity for endostatin was found to have a significantly (P = 0.0069) positive correlation with AS. Significantly high levels of endostatin were noted in patients with trabecular-type tumors (P = 0.0446) and in patients with hepatitis B infection (P = 0.0183). The serum endostatin level was found to be significantly (P = 0.0166) higher in living patients and patients with high serum endostatin levels had a tendency (P = 0.0871) toward long survival. Tissue endostatin expression was found to have a direct correlation with the serum endostatin level (P = 0.0117).


CONCLUSIONS
The measurement of serum endostatin can predict tumor vascularity and may serve as a promising tool in the antiangiogenic therapy for patients with HCC.
Dhar
Dipok Kumar
DK
Second Department of Surgery, Shimane Medical University, Izumo, Japan. nigeka33@shimane-med.ac.jp
Ono
Takashi
T
Yamanoi
Akira
A
Soda
Yukiko
Y
Yamaguchi
Emi
E
Rahman
Md Atikur
MA
Kohno
Hitoshi
H
Nagasue
Naofumi
N
D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000098:blood supply / Q000473:pathology; D003094:Collagen / Q000097:blood*; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000097:blood*; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008099:Liver / Q000098:blood supply; D008113:Liver Neoplasms / Q000097:blood* / Q000098:blood supply / Q000473:pathology; D008222:Lymphokines / Q000097:blood*; D009389:Neovascularization, Pathologic / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043169:Endostatins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D003094:Collagen