Poon R T, Ng I O, Lau C, Zhu L X, Yu W C, Lo C M, Fan S T, Wong J
Centre of Liver Diseases, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Ann Surg. 2001 Feb;233(2):227-35. doi: 10.1097/00000658-200102000-00012.
To evaluate the correlation between serum vascular endothelial growth factor (VEGF) level and the clinicopathologic features in patients with hepatocellular carcinoma (HCC).
VEGF is an important angiogenic factor regulating tumor angiogenesis. A high serum VEGF level has been shown to be associated with tumor progression and metastasis in several human cancers, but its significance in HCC is unclear. The correlation between serum VEGF level and tumor pathologic features in patients with HCC has not been studied before.
Preoperative serum samples and tumor specimens were prospectively collected in 100 patients undergoing resection of HCC. Serum VEGF level was measured by enzyme-linked immunosorbent assay, and tumor VEGF expression was assessed by immunohistochemical study. Histopathologic examination was performed by a pathologist without prior knowledge of the serum VEGF level or tumor VEGF expression.
Preoperative serum VEGF levels ranged from 15 to 1,789 pg/mL (median 269). When serum VEGF levels were compared between groups categorized by different clinicopathologic variables, significant correlation was found between a high serum VEGF level and absence of tumor capsule, presence of intrahepatic metastasis, presence of microscopic venous invasion, and advanced stage. There was a positive correlation between the serum VEGF level and tumor expression of VEGF as well as platelet count. When the 75th percentile serum VEGF level (500 pg/mL) was used as a cutoff level, the frequency of venous invasion in patients with a high serum VEGF level was significantly greater compared with patients with a low serum VEGF level. By multivariate analysis, a serum VEGF level of more than 500 pg/mL and tumor size more than 5 cm were independent preoperative factors predictive of microscopic venous invasion. During a median follow-up of 11.6 months, 48% of patients with a serum VEGF level of more than 500 pg/mL and 27% of those with a serum VEGF level of 500 pg/mL or less developed postoperative recurrence.
These results show that a high preoperative serum VEGF level is a predictor of microscopic venous invasion in HCC, suggesting that the serum VEGF level may be useful as a biologic marker of tumor invasiveness and a prognostic factor in HCC.
评估肝细胞癌（HCC）患者血清血管内皮生长因子（VEGF）水平与临床病理特征之间的相关性。
VEGF是一种调节肿瘤血管生成的重要血管生成因子。在几种人类癌症中，高血清VEGF水平已被证明与肿瘤进展和转移相关，但其在HCC中的意义尚不清楚。此前尚未研究过HCC患者血清VEGF水平与肿瘤病理特征之间的相关性。
前瞻性收集100例行HCC切除术患者的术前血清样本和肿瘤标本。采用酶联免疫吸附测定法测量血清VEGF水平，并通过免疫组织化学研究评估肿瘤VEGF表达。由一名对血清VEGF水平或肿瘤VEGF表达不知情的病理学家进行组织病理学检查。
术前血清VEGF水平范围为15至1789 pg/mL（中位数为269）。当比较按不同临床病理变量分类的组之间的血清VEGF水平时，发现高血清VEGF水平与无肿瘤包膜、存在肝内转移、存在微小静脉侵犯及晚期显著相关。血清VEGF水平与肿瘤VEGF表达以及血小板计数呈正相关。当将第75百分位数血清VEGF水平（500 pg/mL）用作临界值时，高血清VEGF水平患者的静脉侵犯频率显著高于低血清VEGF水平患者。通过多变量分析，血清VEGF水平超过500 pg/mL和肿瘤大小超过5 cm是预测微小静脉侵犯的独立术前因素。在中位随访11.6个月期间，血清VEGF水平超过500 pg/mL的患者中有48%发生术后复发，而血清VEGF水平为500 pg/mL或更低的患者中有27%发生术后复发。
这些结果表明，术前高血清VEGF水平是HCC中微小静脉侵犯的预测指标，提示血清VEGF水平可能作为肿瘤侵袭性的生物学标志物和HCC的预后因素有用。
