Magnetic Resonance Imaging and Expression of Vascular Endothelial Growth Factor in Hepatocellular Nodules in Cirrhosis and Hepatocellular Carcinomas

Abstract

We summarized and discussed our previous research results on correlation between magnetic resonance (MR) imaging findings and vascular endothelial growth factor (VEGF) expression in benign or borderline hepatocellular nodules in cirrhosis, hepatocellular carcinomas (HCCs), and in the surrounding liver. Magnetic resonance images were retrospectively correlated quantitatively and qualitatively with VEGF expression in hepatic nodules and in the surrounding liver. By immunohistochemistry, hepatic nodules with moderate to strong immunoreactivity for VEGF showed higher T1 signal intensity, and those with intense immunoreactivity for VEGF showed higher T2 signal intensity. By Western blotting, HCC-to-liver contrast-to-noise ratio correlated with VEGF indices (VEGFs) of hepatocellular carcinomas inversely on opposed-phase T1-weighted, directly on T2-weighted, and marginally and inversely on gadolinium-enhanced hepatic arterial-phase images. On T2-weighted images, standard-deviation ratio of hepatocellular carcinomas correlated directly with VEGFs of hepatocellular carcinomas. Heterogeneities of hepatocellular carcinomas on MR images correlated directly with VEGFs of HCCs on opposed-phase T1-weighted, T2-weighted, hepatic arterial-phase, and equilibrium-phase images. Our results may reflect that MR signal intensity, hepatic arterial vascularity, and heterogeneity of hepatocellular nodules on MR images are closely related to the intensity of VEGF expression as up-regulated by hyper- or hypoxia in the nodules. Gadolinium-enhanced MR imaging may be useful to monitor ischemic state of hepatocelluar nodules. Although real impacts of our results on radiologic practice have been still debatable, we believe that our results may help future radiologic practice in conjunction with biomolecular or genetic treatments for hepatocellular carcinomas.

MRI findings of rapidly progressive hepatocellular carcinoma

“…Several studies have described the MRI findings that correlate with VEGF expression in cirrhotic liver nodules and HCCs [19][20][21]. These studies revealed that hepatic nodules with moderate to strong immunoreactivity for VEGF showed higher signal intensity on T1-weighted images and those with intense immunoreactivity for VEGF showed higher signal intensity on T2-weighted images [20]. Similar to that study, all our patients showed HCCs with slightly to moderately high signal on T2-weighted images.…”

“…Tumor growth is dependent on a neovascular blood supply or tumor angiogenesis and is related to the production of humoral factors including vascular endothelial growth factor (VEGF). Several studies have described the MRI findings that correlate with VEGF expression in cirrhotic liver nodules and HCCs [19][20][21]. These studies revealed that hepatic nodules with moderate to strong immunoreactivity for VEGF showed higher signal intensity on T1-weighted images and those with intense immunoreactivity for VEGF showed higher signal intensity on T2-weighted images [20].…”

Vascular endothelial growth factor in the management of hepatocellular carcinoma

“…Other studies suggested a correlation between the degree of tissue VEGF expression measured by IHC and intensity of both the magnetic resonance signal and the contrast enhancement of the hepatic artery on computed tomography in patients with HCC using IHC. [32][33][34] Furthermore, recent studies demonstrated a definite correlation between tumor VEGF expression using IHC and microvessel density, which is a marker of tumor angiogenesis. 35,36 Similar findings in other studies have laid the groundwork for using VEGF activity as a tool to screen for both premalignant liver lesions and invasive HCC.…”

Molecular targeted therapy for hepatocellular carcinoma

“…20 Notably, studies have suggested a correlation between the degree of tissue VEGF expression and the intensity of both the magnetic resonance signal and the computed tomographic enhancement of the hepatic artery, which represent radiologic vascular signals. [21][22][23] Hence, the hypervascular nature of HCC has led to increasing interest in exploring the potential of antiangiogenic therapy in this disease. …”