Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere J-F, Benamouzig R, Breau J-L, Perret G-Y
APHP. Department of Oncology, Hôpital Avicenne, Bobigny, France.
Br J Cancer. 2006 Jun 19;94(12):1823-32. doi: 10.1038/sj.bjc.6603176.
We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n = 957) for RFS and 18 for OS (n = 2383) and for VEGF in 17 studies, including nine studies for RFS (n = 1064) and 10 for OS (n = 1301). High MVD significantly predicted poor RFS (RR = 2.32 95% CI: 1.39-3.90; P < 0.001) and OS (RR = 1.44; 95% CI: 1.08-1.92; P = 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR = 2.84; 95% CI: 1.95-4.16) and OS (RR=1.65; 95% CI: 1.27-2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.
我们对所有已发表的研究进行了荟萃分析，这些研究涉及肿瘤内微血管密度（MVD）（45项研究）或血管内皮生长因子（VEGF）表达（27项研究），二者均反映血管生成，与结直肠癌（CRC）的无复发生存期（RFS）和总生存期（OS）相关。对于每项研究，MVD的影响通过以中位MVD为临界值的两种生存分布之间的风险比来衡量。11项研究未提及生存数据或不符合纳入标准，6项是同一系列的多篇发表，因此MVD研究中留下32项独立研究（3496例患者），VEGF研究留下18项独立研究（2050例患者）。微血管密度通过免疫组织化学评估，使用抗VIII因子抗体（16项研究）、CD31抗体（10项研究）或CD34抗体（7项研究）。血管内皮生长因子表达大多通过免疫组织化学评估。对22项研究中的MVD进行了统计分析（其他研究缺乏生存统计数据），其中9项研究（n = 957）用于RFS分析，18项研究（n = 2383）用于OS分析；对17项研究中的VEGF进行了统计分析，其中9项研究用于RFS分析（n = 1064），10项研究用于OS分析（n = 1301）。高MVD显著预示着较差的RFS（RR = 2.32，95%CI：1.39 - 3.90；P < 0.001）和OS（RR = 1.44；95%CI：1.08 - 1.92；P = 0.01）。使用CD31或CD34时，MVD与生存率呈负相关，而使用VIII因子时则不然。血管内皮生长因子表达显著预示着较差的RFS（RR = 2.84；95%CI：1.95 - 4.16）和OS（RR = 1.65；95%CI：1.27 - 2.14）。为了强化我们的研究结果，未来的前瞻性研究应探索MVD或VEGF表达与生存或治疗反应（如抗血管生成治疗）之间的关系。在未来的研究中，应对这些血管生成标志物的评估进行更好的标准化。
