Vascular endothelial growth factor receptor 2 (VEGFr2) expression and recurrence of hepatocellular carcinoma following liver transplantation: The Cleveland Clinic experience

Abstract

4594 Background: The optimal treatment for hepatocellular carcinoma (HCC) for advanced cirrhosis is deceased donor liver transplantation (LT). However, tumor reoccurrence represents major limitation of long term survival. It is, therefore, important to recognize markers which portend poor prognosis including VEGFr2 expression. We examined the association between VEGFr2 expression and tumor recurrence, following liver transplantation in MELD era. Methods: Of 361 consecutive patients who underwent LT at the Cleveland Clinic between June 2002 and August 2006, 126 patients were diagnosed with HCC. Immunohistochemical staining for VEGFr2 was performed in HCC and corresponding adjacent cirrhotic liver from 79 patients out of 126 patients. Stains were scored by estimating percent of positive surface area in veins, arteries, and sinusoidal lining cells of tumor and adjacent tissues. Binary staining variables were created based on median values. Kaplan-Meier survival analysis was used to assess the association between VEGFr2 staining and either recurrence-free survival (RFS) or overall survival (OS). Analysis was only done on 79 patients who had VEGFr2 staining. Results: 87% of the study patients were males. The mean age was 57 (range, 35–76). 1-year and 2-year RFS was 94% and 78%, respectively, as compared to 89% and 79% for the OS. Patients’ death secondary to complication of liver transplant was not censored. Vascular invasion was consistently associated with HCC recurrence (p<0.01) and overall mortality (p<0.05). Subjects with VEGFr2 overexpression in tumor arterioles (p<0.01), venules (p<0.05), or sinusoids (p<0.05) had worse overall survival. In the RFS analysis, similar trends were detected for VEGFr2 overexpression in all three HCC vascular tissues. Higher expression of VEGFr2 in the sinusoids of adjacent non-tumorous liver portended poorer recurrence-free survival (p<0.05). Conclusions: Elevated VEGFr2 expression in HCC was correlated with worse outcome. VEGFr2 inhibitors such as sorafenib may play a role in preventing tumor reoccurrence. No significant financial relationships to disclose.