Correlative study of angiogenesis and dynamic contrast-enhanced magnetic resonance imaging features of hepatocellular carcinoma.
OBJECTIVE
To explore the correlation between contrast-enhancement patterns on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and angiogenesis by analyzing microvessel density (MVD), vascular endothelial growth factor (VEGF), and P53 protein expression in hepatocellular carcinoma (HCC).


METHODS
MRI was performed with a GE Signa 1.5T MR scanner using SE and FMPSPGR sequences in 30 patients (38 lesions) during the period October 1998 to March 2000. All had histopathologically proven HCC. MR images were reviewed/ analyzed retrospectively. The 30 patients were between 35 and 65 years of age (average age 58; 18 M and 12 F). SE T1WI, PDWI, and T2WI were acquired initially. The FMPSPGR sequence was acquired in the same position. The DCE-MRI was performed in the arterial, portal vein, and delay phase after a bolus injection of Gd-DTPA. The specimens were stained immunohistochemically for CD34, VEGF, and P53. MVD was highlighted by anti-CD34 antibody staining. The enhancement features of HCC lesions were studied correlatively with the tumor MVD, VEGF, and P53 expression at protein level.


RESULTS
In the arterial phase, the results showed that MVD of HCC in the high-enhancement group (229.76 +/- 80.96) was higher than that in the equal-enhancement (173.09 +/- 61.38) and low-enhancement groups (153.00 +/- 108.58) (P < 0.01, respectively). VEGF expression of HCC in the high-enhancement group (68.42%) was higher than that in the equal-enhancement (36.36%) and low-enhancement groups (38.89%) (P < 0.05, respectively). In the portal vein phase, MVD of HCC in the enhancement group (259.80 +/- 93.30) was higher than that in the non-enhancement group (178.64 +/- 92.65) (P < 0.05). No significant correlation was found between VEGF expression and the enhancement feature in the portal vein phase. In the delay phase, MVD of HCC in the ring-enhancement group (269.06 +/- 57.89) was significantly higher than that in the non-ring-enhancement group (144.10 +/- 88.90) (P < 0.01). There was a significant difference in VEGF expression between the ring-enhancement group (76.47%) and the non-ring-enhancement group (42.86%) (P < 0.05). No significant correlation was detected between P53 protein expression and the enhancement feature. Relative enhancement (RE) correlated with MVD, but not with VEGF and P53 protein expression.


CONCLUSIONS
The contrast-enhancement patterns on DCE-MRI are influenced by tumor angiogenesis, as reflected by elevated VEGF expression, and are therefore valuable indicators for accessing tumor angiogenic activity and tumor neovascularization in vivo in HCC patients.
Wang
B
B
Department of Radiology, Medical Imaging Center of the Affiliated Hospital, Department of Medical Biology, Weifang Medical University, Weifang, P R China. binwang001@yahoo.com.cn
Gao
Z Q
ZQ
Yan
X
X
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000175:diagnosis*; D016009:Chi-Square Distribution; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply* / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D015588:Observer Variation; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D003287:Contrast Media; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D019786:Gadolinium DTPA