Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma.
OBJECTIVE
Vascular endothelial growth factor-C (VEGF-C) is thought to be an important factor in tumor angiogenesis/lymphangiogenesis, but its role in hepatocellular carcinoma (HCC) has not yet been fully investigated.


METHODS
We immunohistochemically examined VEGF-C expression in surgically resected tissues of 90 HCC.


RESULTS
In the 78 HCC with a single histological grade, VEGF-C expression was significantly stronger in poorly differentiated HCC than in well- (P=0.003) or moderately differentiated HCC (P=0.0002). A 'nodule-in-nodule' case presented VEGF-A expression in the well-differentiated component and VEGF-C expression in the moderately-poorly differentiated component. According to nodular diameter, VEGF-C expression was significantly higher in nodules of 3.0 cm or larger (P=0.0263). Extrahepatic metastases seen in seven cases expressed VEGF-C. In 20 of the 28 cases who were able to be followed up, the frequency of intrahepatic recurrence tended to be higher and extrahepatic metastasis was significantly higher in the cases who had VEGF-C expression in the tumor casts of the intrahepatic portal/hepatic vein branches than other cases without the expression (P=0.0139). Disease-free survival time tended to be shorter in cases with VEGF-C expression in tumor casts of the portal/hepatic vein than in those without VEGF-C expression (P=0.053; log-rank test).


CONCLUSIONS
VEGF-C expression is related to the progression of HCC, and VEGF-C expression in tumor casts of the intrahepatic portal/hepatic vein is considered to be a factor indicating recurrence/metastasis sites.
Yamaguchi
Rin
R
Department of Pathology, Research Center of Innovative Cancer Therapy of the 21 Century COE Program for Medical Science, Kurume University School of Medicine, Kurume, Japan. rin@med.kurume-u.ac.jp
Yano
Hirohisa
H
Nakashima
Osamu
O
Akiba
Jun
J
Nishida
Naoyo
N
Kurogi
Mina
M
Kojiro
Masamichi
M
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D018572:Disease-Free Survival; D005260:Female; D006503:Hepatic Veins / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011169:Portal Vein / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C