Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma.
OBJECTIVE
Angiogenesis plays an important role in tumor growth and metastasis. It is regulated by angiogenic factors. Thymidine phosphorylase (platelet-derived endothelial cell growth factor) is one such factor. Although the significance of platelet-derived endothelial cell growth factor has been studied for several types of tumor, the expression of platelet-derived endothelial cell growth factor and its correlation with microvessel density or clinicopathological factors in hepatocellular carcinoma are unknown. We evaluated microvessel density and platelet-derived endothelial cell growth factor expression in hepatocellular carcinoma to determine whether microvessel density and platelet-derived endothelial cell growth factor expression are correlated with the clinicopathological factors of hepatocellular carcinoma.


METHODS
Using immunohistochemical staining with anti-platelet-derived endothelial cell growth factor antibody and the ELISA method, we evaluated the correlation among platelet-derived endothelial cell growth factor expression, microvessel density and clinicopathological factors in 84 hepatocellular carcinoma patients. Microvessels were stained with anti-human von Willebrand factor (anti-Factor VIII) and anti-CD34.


RESULTS
In the surrounding liver, there was a significant correlation between microvessel density and platelet-derived endothelial cell growth factor expression (p=0.002), and hepatitis C virus-positive livers had higher microvessel densities than otherwise (p=0.003). However, this correlation was not found for hepatocellular carcinoma, but hepatitis C virus-positive tumors had higher expression of platelet-derived endothelial cell growth factor (p=0.018). Microvessel density in hepatocellular carcinoma obtained by Factor VIII staining inversely affected the recurrence-free survival rate (p=0.0416), but the microvessel density by CD34 staining was not a significant predictor.


CONCLUSIONS
This study indicates that platelet-derived endothelial cell growth factor may not be a major regulator of angiogenesis of hepatocellular carcinoma, but this enzyme may play an important role in hepatocarcinogenesis cooperating with hepatitis C virus. Also, the density, not of sinusoid-like vessels, but of larger vessels in hepatocellular carcinoma could be a prognostic factor for hepatocellular carcinoma.
Yamamoto
A
A
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Dhar
D K
DK
El-Assal
O N
ON
Igarashi
M
M
Tabara
H
H
Nagasue
N
N
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008833:Microcirculation / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011237:Predictive Value of Tests; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000032:analysis*; D013997:Time Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis
D015703:Antigens, CD; D018952:Antigens, CD34; D014841:von Willebrand Factor; D013939:Thymidine Phosphorylase