Preoperative serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study

Abstract

OBJECTIVE: To evaluate the correlation between preoperative serum vascular endothelial growth factor (VEGF) level and clinicopathologic features in hepatocellular carcinoma (HCC). BACKGROUND DATA: VEGF is the most potent angiogenic factor regulating tumor angiogenesis. A high serum VEGF level has been shown to be associated with tumor invasion and metastasis in several human cancers, but its significance in HCC remains unclear. The correlation between serum VEGF level and tumor pathologic features in HCC has not been studied before. Patients and Methods: Preoperative serum samples and resected tumor specimens were prospectively collected in 100 patients undergoing resection of HCC. Serum VEGF level was measured by enzyme-linked immunosorbent assay, and VEGF expression in tumors was assessed by immunohistochemical study. Histopathological examination was carried out by a pathologist without prior knowledge of serum VEGF level or tumor VEGF expression. Results: The median serum VEGF level among 100 patients with HCC was 260.8 pg/ml (range 24.9 - 1788.8 pg/ml), significantly higher than that of 20 normal control subjects (median 179.8, range 40.6 - 670.5 pg/ml, p =0 0.038). When median serum VEGF levels were compared by different clinicopathologic variables, significant correlation was found between a high serum VEGF level and absence of tumor capsule (p =0 0.023), presence of intrahepatic metastasis (p =0 0.019), microscopic venous invasion (p < 0.001) and advanced pTNM stage (p =0 0.001). Serum VEGF level was positively related to tumor expression of VEGF (p =0 0.025) and platelet count (p =0 0.001). When the 75th percentile serum VEGF level (500 pglml) was used as a cut-off level, the incidence of microscopic venous invasion in patients with a serum VEGF level > 500 pglml was significantly higher compared with those with a serum VEGF level :s 500 pglml (72% vs. 32%, P < 0.001). By multivariate analysis of various preoperative parameters, preoperative serum VEGF level> 500 pg/ml (risk ratio 4.3077, p =0 0.016) and tumor size> 5 em (risk ratio 5.9778, p < 0.001) were independent factors predictive of microscopic venous invasion. Conclusions: A high preoperative serum VEGF level correlates with microscopic venous invasion and intrahepatic metastasis in HCe. Serum VEGF level may be useful as a biological marker of tumor invasiveness in HCC.