Zhang Jun, Jia Zhiliang, Li Qiang, Wang Liwei, Rashid Asif, Zhu Zhenggang, Evans Douglas B, Vauthey Jean-Nicolas, Xie Keping, Yao James C
Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2007 Apr 15;109(8):1478-86. doi: 10.1002/cncr.22554.
Vascular endothelial growth factor (VEGF) is a critical proangiogenic factor in solid tumors. However, its expression and role in human neuroendocrine tumor development and progression remains unclear.
Using immunohistochemistry, VEGF and Sp1 expression patterns were investigated in 50 cases of human gastrointestinal neuroendocrine tumor having various clinicopathologic characteristics.
It was found that strong VEGF expression was detected in tumor cells, whereas no or very weak VEGF expression was detected in stromal cells surrounding or within the tumors. The levels of VEGF expression directly correlated with the expression levels of Sp1 and microvessel density. Strong, weak, and negative VEGF expression was observed in 32%, 54%, and 14% of cases, respectively. Compared with the group with negative VEGF expression, VEGF (weak/strong) expression was associated with metastasis (14% versus 58%; P = .03). The median progression-free survival (PFS) durations of patients with strong and weak VEGF expression were 29 months and 81 months, respectively. With a median follow-up duration of 50 months, the median PFS duration for the group with negative VEGF expression has not been reached. Compared with the log-rank test, VEGF expression was associated with poor PFS (P = .02). Using in vitro and in vivo models, human carcinoid cell lines were treated with bevacizumab, a monoclonal antibody targeting VEGF. Bevacizumab did not inhibit the growth of carcinoid cells in vitro but significantly reduced tumor angiogenesis and impaired tumor growth in animals.
The data suggest that overexpression of VEGF promotes the growth of human neuroendocrine tumors in part through up-regulation of angiogenesis.
血管内皮生长因子（VEGF）是实体瘤中一种关键的促血管生成因子。然而，其在人类神经内分泌肿瘤发生发展中的表达及作用仍不清楚。
采用免疫组织化学方法，对50例具有不同临床病理特征的人类胃肠道神经内分泌肿瘤进行VEGF和Sp1表达模式研究。
发现肿瘤细胞中检测到强VEGF表达，而肿瘤周围或内部的基质细胞中未检测到或仅检测到非常弱的VEGF表达。VEGF表达水平与Sp1表达水平和微血管密度直接相关。分别在32%、54%和14%的病例中观察到VEGF强、弱和阴性表达。与VEGF阴性表达组相比，VEGF（弱/强）表达与转移相关（14%对58%；P = 0.03）。VEGF强表达和弱表达患者的无进展生存期（PFS）中位数分别为29个月和81个月。中位随访时间为50个月，VEGF阴性表达组的中位PFS持续时间尚未达到。与对数秩检验相比，VEGF表达与不良PFS相关（P = 0.02）。使用体外和体内模型，用靶向VEGF的单克隆抗体贝伐单抗处理人类类癌细胞系。贝伐单抗在体外不抑制类癌细胞的生长，但在动物体内显著减少肿瘤血管生成并损害肿瘤生长。
数据表明，VEGF的过表达部分通过上调血管生成促进人类神经内分泌肿瘤的生长。
