Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens.
BACKGROUND
Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours.


METHODS
Using nested reverse-transcription-polymerase chain reaction, we examined the biopsy specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis, for the expression of hepatic VEGF, and the VEGF receptors KDR and fit-1. To avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we used biopsy specimens of the liver instead of resected specimens.


RESULTS
Vascular endothelial growth factor mRNA expression was detected in the tumour portion of the specimens in 13 of 14 patients (93%), and in the corresponding non-tumour portion of the specimens in eight patients (57%; P= 0.08). No differences were found between the tumour portion and the corresponding non-tumour portion in relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF receptors, KDR and fit-1, was detected in 14 (100%) and 11 (79%) of the tumour portions, respectively, and in four (29%) and five (36%) of the corresponding non-tumour portions, respectively (chi2 test: KDR, P< 0.01; fit-1, P= 0.08). The relative concentration of KDR mRNA in the tumour portions was significantly higher than in the non-tumour portions (Mann-Whitney U-test: P<0.001) but no differences were detected for fit-1.


CONCLUSIONS
KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF.
Third Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
T
T
Shimamura
S
S
Saito
K
K
Morita
T
T
Kitamura
M
M
Morimoto
T
T
Kiba
K
K
Numata
K
K
Tanaka
H
H
Sekihara
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000737:chemistry*; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000737:chemistry*; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D017978:Receptors, Growth Factor / Q000032:analysis*; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor