Koutsimpelas D, Bjelopavlovic M, Yetis R, Frauenknecht K, Adryan B, Schmidtmann I, Gouveris H, Fruth K, Heinrich U R, Stauber R H, Mann W J, Brieger J
Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
ORL J Otorhinolaryngol Relat Spec. 2012;74(6):330-8. doi: 10.1159/000346238. Epub 2013 Jan 19.
BACKGROUND/AIMS: The molecular mechanisms downstream of mutated neurofibromatosis type 2 (NF2) gene resulting in the growth and development of vestibular schwannoma (VS) are controversial. Several lines of evidence suggest the involvement of the vascular endothelial growth factor (VEGF) pathway in VS development. Given that recent studies of VEGF blockade in patients with NF2-associated VS showed positive effects on VS growth control, we initiated this comprehensive study of the VEGF pathway in sporadic VS.
A tissue microarray analysis of 182 sporadic VS was conducted. The expression of VEGF and its receptors as well as the proliferative activity of the tumors were quantified. The expression data were correlated to tumor volumes and diameters as well as to tumor recurrence and previous irradiation.
All studied tumors expressed VEGF and its receptors. Proliferative activity was related to the growth characteristics of the tumors. Moreover, we found significantly higher VEGF levels in recurrent tumors (p = 0.0387) and in preoperatively irradiated tumors (p = 0.0213).
Our data suggest a relevant role of the VEGF pathway in VS growth and therapy outcome. Therefore, targeting this pathway using antiangiogenic compounds might be beneficial for patients with sporadic VS, especially those with recurrent or irradiated tumors.
背景/目的：导致前庭神经鞘瘤（VS）生长和发展的2型神经纤维瘤病（NF2）基因突变的下游分子机制存在争议。多项证据表明血管内皮生长因子（VEGF）通路参与了VS的发展。鉴于最近对NF2相关VS患者进行的VEGF阻断研究显示对VS生长控制有积极作用，我们启动了对散发性VS中VEGF通路的这项全面研究。
对182例散发性VS进行组织芯片分析。对VEGF及其受体的表达以及肿瘤的增殖活性进行定量分析。将表达数据与肿瘤体积、直径以及肿瘤复发和既往放疗情况相关联。
所有研究的肿瘤均表达VEGF及其受体。增殖活性与肿瘤的生长特征相关。此外，我们发现复发性肿瘤（p = 0.0387）和术前接受放疗的肿瘤（p = 0.0213）中的VEGF水平显著更高。
我们的数据表明VEGF通路在VS生长和治疗结果中具有重要作用。因此，使用抗血管生成化合物靶向该通路可能对散发性VS患者有益，尤其是那些患有复发性或接受过放疗的肿瘤患者。
