Prominent vascular endothelial proliferation in clinically aggressive neuroblastoma

Abstract

10611 Background: Tumor blood vessels are disorganized and vascular endothelial cell proliferation (VEP) has been identified as a poor prognosticator in many adult cancers. To determine the clinical significance of VEP in neuroblastoma (NB), we evaluated blood vessel architecture in tumor sections from 51 children diagnosed at Children's Memorial Hospital, Chicago (CMH) and in 154 NB tumors on a Tissue Microarray (TMA) constructed at Children's Hospital of Philadelphia (CHOP). Methods: H&E-stained tumor sections were examined for the presence of structurally abnormal vessels and further characterized by immunostaining with anti-CD31 and von Willebrand factor (vWF) antibody to highlight endothelial cells. Tumors that contained vessels with disorganized walls and more than one endothelial cell layer were classified as VEP positive. Tumor sections that contained only thin walled vessels with no more than one layer of endothelial cells were classified as VEP negative. Associations between VEP and established clinico-pathologic features and outcome were assessed. Results: In the CHOP series, VEP was associated with high-risk group classification and MYCN amplification (p<0.001 and p=0.006). In the CMH series only 5 of the 10 children with MYCN amplification had VEP but 4 of these 5 patients have died, while there were no deaths in the subset of patients with MYCN amplified tumors that lacked VEP (n=5). In both study groups, VEP was significantly associated with Schwannian stroma-poor histology (CMH series: p=0.008; CHOP series: p<0.001) and decreased survival probability (CMH series: p=0.017; CHOP series: p= 0.014). Conclusions: The association between structurally abnormal vessels and poor outcome provides further support for the concept that angiogenesis plays an important role in determining the biologic behavior of NB tumors. Our results also indicate that angiogenesis is regulated differently in Schwannian stroma-rich versus stroma-poor NB tumors. Further studies investigating the activity of angiogenic inhibitors in children with clinically aggressive stroma-poor NB are warranted. No significant financial relationships to disclose.