Differential vascular endothelial growth factor A protein expression between small hepatocellular carcinoma and cirrhosis correlates with serum vascular endothelial growth factor A and α-fetoprotein

Drugs with antivascular endothelial growth factor A (anti-VEGF-A) action are under clinical evaluation with encouraging results in advanced hepatocellular carcinoma (HCC). The relative VEGF-A protein expression in non-advanced HCC and in the cirrhotic non-tumoral tissue in the same patient, a variable that could be important for treatment efficacy, has been investigated with conflicting results, only using the cirrhotic tissue surrounding the neoplasm (CS). We measured, for the first time, VEGF-A expression in non-advanced HCC and in the respective CS and cirrhotic tissue at a distance from the tumour (CD), in 24 patients who underwent liver transplantation. VEGF-A protein was more expressed (P < 0.05) in HCC than in CD, while no difference was found between HCC and CS. In HCC patients with a serum alpha-fetoprotein (AFP) higher than 20 ng/ml, VEGF-A protein expression in HCC was higher than in the corresponding CD in 83% of cases and AFP and serum VEGF-A corrected for the platelet count positively correlated with the differential VEGF-A protein expression between HCC and CD. Our data provide a rationale for clinical trials involving anti-VEGF-A treatments in patients with non-advanced HCC, and suggest that serum AFP and VEGF-A are variables to be taken into account in these studies.