A Pilot Study of Vasculogenic Mimicry Immunohistochemical Expression in Hepatocellular Carcinoma

Context.—The “de novo” formation of fluid-conducting patterns by tumor cells, termed vasculogenic mimicry (VM), is associated with increased mortality in many different solid tumors. Objective.—To identify VM patterns in hepatocellular carcinoma (HCC) and to determine whether these patterns were associated with more rapid tumor recurrence after orthotopic liver transplantation. Design.—Subjects included 20 patients who underwent orthotopic liver transplantation and were found to have HCC in the liver explant. Samples from 5 normal postmortem livers and 5 explanted livers with hepatitis C virus cirrhosis without HCC served as control tissues. Patterned matrix VM expression in HCC was identified by the presence of laminin-positive loops surrounding packets of tumor cells. Time to HCC recurrence after orthotopic liver transplantation was compared between patients with and without patterned VM expression. The relationships among VM in HCC, cause of chronic liver disease, serum α-fetoprotein level at the time of diagnosis, tissue expression by epidermal growth factor receptor, and endothelial markers including vascular endothelial growth factor and CD31 were assessed. Results.—Patterned matrix VM was identified in 11 of 20 primary HCC tissue samples. Vasculogenic mimicry was absent in all 10 control cases and was not identified in any area of dysplasia. The expression of VM in HCC lesions in liver explants was associated with more rapid posttransplant recurrence (P = .01). Vasculogenic mimicry was not associated with the cause of liver disease, serum α-fetoprotein level at time of diagnosis, or expression of epidermal growth factor receptor, vascular endothelial growth factor, or CD31. Conclusions.—Vasculogenic mimicry of the patterned matrix type is present in hepatocellular carcinoma and is associated with tumor recurrence after orthotopic liver transplantation. Vasculogenic mimicry lesions are not associated with endothelial markers in HCC.