This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Peddinti, R. Articles by Cohn, S. L. Search for Related Content PubMed PubMed Citation Articles by Peddinti, R. Articles by Cohn, S. L.

Prominent Microvascular Proliferation in Clinically Aggressive Neuroblastoma

Authors' Affiliations: ¹ Department of Pediatrics, Children's Memorial Hospital; ² Robert H. Lurie Comprehensive Cancer Center, Northwestern University; ³ Institute for Molecular Pediatric Sciences, University of Chicago, Chicago, Illinois; ⁴ Department of Pediatrics, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and ⁵ Department of Pathology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota

Requests for reprints: Susan L. Cohn, Clinical Sciences, Institute for Molecular Pediatric Sciences, University of Chicago, 5841 Maryland Avenue, MC 4060, Room N114, Chicago, IL 60637. Phone: 773-702-2571; Fax: 773-834-1329; E-mail: scohn{at}peds.bsd.uchicago.edu.

Purpose: Tumor vasculature is disorganized and glomeruloid microvascular proliferation (MVP) has been identified as a poor prognosticator in some adult cancers. To determine the clinical significance of MVP, including glomeruloid MVP in neuroblastoma, we initially examined vessel architecture in tumor sections from 51 children diagnosed at Children's Memorial Hospital (CMH) and subsequently evaluated 154 neuroblastoma tumors on a tissue microarray constructed at Children's Hospital of Philadelphia (CHOP).

Experimental Design: H&E sections were examined for the presence of structurally abnormal vessels and further characterized by immunostaining for CD31 and von Willebrand factor to highlight endothelial cells and -smooth muscle actin for pericytes. Tumors with thickened walls containing a complete layer of hypertrophic endothelial cells plus additional layers of vascular mural cells were classified as MVP positive. Associations between MVP and established clinicopathologic features and outcome were assessed.

Results: In both series, MVP was significantly associated with Schwannian stroma-poor histology (CMH, P = 0.008; CHOP, P < 0.001) and decreased survival probability (CMH, P = 0.017; CHOP, P = 0.014). In the CHOP series, MVP was associated with high-risk group classification (P < 0.001), although this association was not seen in the smaller CMH cohort.

Conclusions: The association between MVP and poor outcome provides further support for the concept that angiogenesis plays an important role in determining the biological behavior of neuroblastoma tumors. Our results also indicate that angiogenesis is regulated differently in Schwannian stroma-rich versus stroma-poor neuroblastoma tumors. Further studies investigating the activity of angiogenic inhibitors in children with clinically aggressive stroma-poor neuroblastoma are warranted.