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

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.