Hepatocellular carcinomas in cirrhotic and noncirrhotic human livers share angiogenic characteristics.
BACKGROUND
The antiangiogenic drug sorafenib has been shown to be an effective treatment for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. It might also be effective in noncirrhotic HCC provided that the angiogenic properties of both tumor types are comparable. The aim of this study is to compare endothelial cell dynamics, microvessel density (MVD), and vessel maturation as indirect markers of angiogenesis in human HCC in cirrhotic and noncirrhotic livers.


METHODS
In a tertiary care setting, 70 consecutive HCC tumors were analyzed for endothelial cell dynamics. CD34 was applied to identify tumor microvessels, double immunolabeling Ki67/CD34 and activated caspase-3/CD34 to assess endothelial cell proliferation and apoptosis, and alpha-smooth muscle actin/CD34 for pericyte coverage. These characteristics were compared in cirrhotic (n = 33) and noncirrhotic HCCs (n = 37). Microvessel density was correlated with radiological signs of hypervascularity as obtained with dynamic four-phase CT scans during the arterial and portal phase of contrast enhancement.


RESULTS
Microvessels in cirrhotic and noncirrhotic HCC were mainly mature. In both groups endothelial cell turnover was low and MVD was not different. There was no correlation between MVD and venous invasion, tumor size, and turnover of tumor cells or endothelial cells. MVD was negatively correlated with contrast washout in the portal venous phase of CT scanning. In transplanted patients, MVD was not correlated with survival, whereas in patients after liver resection a high MVD was associated with a better prognosis.


CONCLUSIONS
Angiogenic characteristics of HCC in cirrhotic and noncirrhotic livers have a remarkable similarity.
Zeng
Wenjiao
W
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gouw
Annette S H
AS
van den Heuvel
Marius C
MC
Molema
Grietje
G
Poppema
Sibrand
S
van der Jagt
Eric J
EJ
de Jong
Koert P
KP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D008113:Liver Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D011859:Radiography; D016019:Survival Analysis
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D053148:Caspase 3