Angiogenesis in hepatocellular carcinoma as evaluated by alpha smooth muscle actin immunohistochemistry

Background/Aims: Angiogenesis has been known to be associated with tumor de velopment. In this study, neovascularization in small hepatocellular carcin oma was investigated by evaluation of intratumoral arteriole counts, using alpha smooth muscle actin antibody immunohistochemistry. Methodology: Surgical specimens from 38 patients with small hepatocellular carcinoma were immunostained for alpha smooth muscle actin and proliferatin g cell nuclear antigen. The correlation between intratumoral arteriole dens ity and clinicopathological factors including angiographic findings, prolif erative activity, and patient prognosis were analyzed. Results: Significant difference in intratumoral arteriole density were obse rved between well-differentiated hepatocellular carcinoma and poorly differ entiated hepatocellular carcinoma (P=0.004) or moderately differentiated he patocellular carcinoma and poorly differentiated hepatocellular carcinoma ( P=0.011). The mean intratumoral arteriole count in the tumors showing angio graphic hypervascularity was significantly higher than that in the tumors w ithout angiographic hypervascularity (P=0.011). A significant and positive correlation was found between proliferating cell nuclear antigen labeling i ndex and intratumoral arteriole density (r=0.5232, P=0.001). A high intratu moral arteriole density in tumor was significantly correlated with shorter patients survival (P=0.018). Cox's multivariate regression analysis showed that the intratumoral arteriole density was independent prognostic factors (P=0.0306). Conclusions: Intratumoral arteriole density was found to be significantly a ssociated with histological grade, proliferative activity, and patient surv ival. It also reflected the angiographic findings. Alpha smooth muscle acti n antibody immunohistochemistry would provide a simple and biologically sig nificant method which is usable to screen neovascularization and arterial b lood supply in hepatocellular carcinoma, and may have predicting utility fo r patients outcome. This technique is applicable to routine paraffin sectio ns, and may be useful as an adjunct to surgical pathology of hepatocellular carcinoma.