Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma.
BACKGROUND
Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are unclear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liver diseases.


METHODS
Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavidin peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay.


RESULTS
The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P<0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant difference was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tissues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the metastasis and recurrence of tumors.


CONCLUSIONS
The high expression of VEGF and abnormality of tissue MVD are useful predictors for vascular invasion and metastasis of liver tumors.
Yao
Deng-Fu
DF
Research Center of Clinical Molecular Biology, Affiliated Hospital of Nantong University, Nantong 226001, China. dfyrcmb@yahoo.com
Wu
Xin-Hua
XH
Zhu
Yong
Y
Shi
Gong-Sheng
GS
Dong
Zhi-Zhen
ZZ
Yao
Deng-Bing
DB
Wu
Wei
W
Qiu
Li-Wei
LW
Meng
Xian-Yong
XY
D000328:Adult; D000368:Aged; D043168:Angiostatins / Q000032:analysis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002199:Capillary Permeability; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000032:analysis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000378:metabolism
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D043168:Angiostatins