title: Prominent microvascular proliferation in clinically aggressive neuroblastoma.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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 alpha-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.
authors.affiliation: Department of Pediatrics, Children's Memorial Hospital, Chicago, Illinois, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Peddinti
authors.forename: Rana
authors.initials: R
authors.lastname: Zeine
authors.forename: Dragos
authors.initials: D
authors.lastname: Luca
authors.forename: Roopa
authors.initials: R
authors.lastname: Seshadri
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chlenski
authors.forename: Kristina
authors.initials: K
authors.lastname: Cole
authors.forename: Bruce
authors.initials: B
authors.lastname: Pawel
authors.forename: Helen R
authors.initials: HR
authors.lastname: Salwen
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
mesh_terms: D002648:Child; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009447:Neuroblastoma / Q000098:blood supply* / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis