Overexpression of VEGF is associated with positive p53 immunostaining in hepatocellular carcinoma (HCC) and adverse outcome of HCC patients

Abstract Background and Objectives To elucidate the clinicopathological correlations among vascular endothelial growth factor (VEGF), microvessel density (MVD) and tumor suppressor gene p53 in hepatocellular carcinomas (HCCs), we adopted a new definition of “VEGF overexpression.” Methods The expressions of VEGF, MVD, and p53 in 113 HCC specimens were analyzed by immunohistochemistry. Results VEGF expression in surrounding liver tended to be stronger (VEGF overexpression, 31%) than, or similar to (57%) that in HCCs ( P = 0.001). P53 positivity was noted in 42 cases (37.1%). MVD ranged from 22 to 201 microvessels/field determined for 5 high‐power fields. VEGF expression in HCCs was positively correlated with MVD ( P = 0.001). VEGF overexpression is positively correlated with young age ( P = 0.008), male gender ( P = 0.01), hepatitis B viremia ( P = 0.013), high α‐fetoprotein levels ( P < 0.001), p53 (+) ( P = 0.036), advanced‐stage HCC ( P = 0.015), and HCC dedifferentiation ( P = 0.004). Survival analyses indicated that VEGF overexpression, high MVD, and advanced‐stage HCC were independent poor prognostic factors for disease‐free and overall survival. Conclusion This study provides evidence of a positive association between parameters reflective of angiogenesis, and p53 expression in HCCs. VEGF overexpression exhibited a significant correlation with viremia and survival. J. Surg. Oncol. 2008;98:349–357. © 2008 Wiley‐Liss, Inc.