Expression of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma and the Surrounding Liver and Correlation with MRI Findings

Abstract

The purpose of our study was to assess the correlation between the quantitative and qualitative imaging findings on unenhanced and gadolinium-enhanced MR images and the intensity of vascular endothelial growth factor (VEGF) expression in hepatocellular carcinomas and in the surrounding nontumorous liver. The intensities of VEGF expression in hepatocellular carcinoma and in the surrounding liver by Western blot analysis were converted to VEGF expression indexes (VEGF(IND)) in 22 surgical specimens ranging in size from 14 to 126 mm (mean, 47.6 +/- 29.5 mm) that were resected in 22 patients (17 men and five women; age range, 41-85 years [mean, 64 years]) between April 2000 and October 2002. MR images were retrospectively evaluated to determine contrast-to-noise ratios (CNRs), signal intensity SD ratios, and phase-shift indexes. Signal intensity characteristics of hepatocellular carcinomas were reviewed independently by two experienced radiologists who were unaware of the pathologic diagnosis or the results of immunoblotting. CNRs, SD ratios, and phase-shift indexes were correlated with VEGF(IND) using a simple regression test, and signal intensity characteristics were correlated with VEGF(IND) using the Spearman's rank correlation test. On opposed-phase T1-weighted spoiled gradient-recalled echo (GRE) images, CNRs correlated inversely with the VEGF(IND) of hepatocellular carcinomas (r = -0.46, p = 0.038). CNRs on T2-weighted fast spin-echo images correlated directly with the VEGF(IND) of hepatocellular carcinomas (r = 0.49, p = 0.025), and on gadolinium-enhanced hepatic arterial phase GRE images marginally and inversely correlated with VEGF(IND) (r = -0.39, p = 0.081). On T2-weighted fast spin-echo images, SD ratios correlated directly with the VEGF(IND) of hepatocellular carcinomas (r = 0.44, p = 0.044). No correlation was found between phase-shift indexes and VEGF expression. The qualitatively assessed signal intensity heterogeneities of hepatocellular carcinomas correlated directly with the VEGF(IND) of hepatocellular carcinomas on opposed-phase T1-weighted GRE, T2-weighted fast spin-echo, hepatic arterial phase GRE, and equilibrium phase GRE images. Our results indicate that the signal intensity and heterogeneity of hepatocellular carcinomas on MR images correlate with the degree of VEGF expression in hepatocellular carcinomas.