Co-expression of Bcl-2 protein and vascular endothelial growth factor in hepatocellular carcinomas treated by chemoembolization

Aims/Background: Transcatheter arterial chemoembolization (TAE) of hepatoce llular carcinoma (HCC) causes anoxia. Escape of cancer cells from anoxic in jury may be enhanced by induction of proteins which provide resistance to a poptosis. Methods: We examined HCCs immunohistochemically for Bcl-2, vascul ar endothelial growth factor (VEGF), p53, and Ki67. The staining intensity for VEGF, a protein induced by anoxia, was assessed morphometrically with a computer-assisted image-analyzer. Results: The frequency of Bcl-2 positive cells was higher in HCCs that had undergone TAE (TAE HCC) than that in HCC s that had not undergone TAE (41.75+/-15.06 vs. 1.01+/-0.79 cells/1000 cell s, p=0.0173). The frequency of p53- or Ki67-positive cells was not increase d after TAE. Of 12 TAE HCCs, 7 had Bcl-2 positive HCC cells and 6 had clust ers of Bcl-2 positive cells. In contrast, 2 of 11 HCCs that had not undergo ne TAE had only a few, sporadically distributed, Bcl-2-positive cells. The staining intensity for VEGF was higher in Bcl-2 positive than in Bcl-2 nega tive areas (1.208+/-0.091 vs. 1.071+/-0.017, p=0.0222). Furthermore, the VE GF staining intensity in Bcl-2 positive al-eas of TAE HCCs was higher than in Bcl-2 negative areas (1.296+/-0.126 vs. 1.1066+/-0.024, p= 0.0186), whil e in HCCs that had not undergone TAE the staining intensity was similar. Co nclusions: TAE of HCC can induce Bcl-2 expression, possibly through anoxic stress.