Hepatocellular Carcinomas in Cirrhotic and Noncirrhotic Human Livers Share Angiogenic Characteristics

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.

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.

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.

Angiogenic characteristics of HCC in cirrhotic and noncirrhotic livers have a remarkable similarity.