title: Angiogenin up-regulation correlates with adverse clinicopathological and biological factors, increased microvascular density and poor patient outcome in neuroblastomas.
abstract: OBJECTIVE
  As new biomarkers are urgently needed to identify children with high-risk neuroblastoma (NB), we studied the contribution of angiogenin (ANG) to angiogenesis and its association with clinicopathological and biological features and patient outcome in NB.
  
  
  RESULTS
  Ninety NBs and 12 ganglioneuromas (GNs) were immunostained for ANG and CD31. ANG expression in NB tumoral cells (ANG scores) and vessels [ANG microvascular density (MVD)] and total MVD (CD31 MVD) were determined. The ANG score was significantly greater in NBs than in GNs (P = 0.015) and in NBs from children with stage 4 tumours, high-risk disease, unfavourable pathology (P < 0.001 for each), MYCN amplification (P = 0.003), and 1p deletion (P = 0.002). ANG scores correlated with ANG MVD and CD31 MVD (P < 0.001 for each). Total ANG and CD31 protein levels, measured with a sensitive enzyme-linked immunosorbent assay, were highly correlated (P = 0.003). High ANG scores were associated with decreased overall and event-free survival (log-rank test, P = 0.025 and P = 0.018, respectively). High ANG MVD was associated with decreased overall and event-free survival (log-rank test, P = 0.009 and P = 0.026, respectively). High CD31 MVD was associated with decreased event-free survival (P = 0.045).
  
  
  CONCLUSIONS
  The strong correlation of ANG up-regulation with total MVD and adverse clinicopathological and biological factors indicates that ANG supports growth and progression in NB.
authors.affiliation: Department of Histopathology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Josiah V
authors.initials: JV
authors.lastname: Dungwa
authors.forename: Urmila
authors.initials: U
authors.lastname: Uparkar
authors.forename: Margaret T
authors.initials: MT
authors.lastname: May
authors.forename: Pramila
authors.initials: P
authors.lastname: Ramani
mesh_terms: D000008:Abdominal Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000401:mortality; D000293:Adolescent; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005729:Ganglioneuroma / Q000098:blood supply / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000098:blood supply / Q000175:diagnosis* / Q000401:mortality; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D015996:Survival Rate; D006113:United Kingdom / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C046366:angiogenin; D012259:Ribonuclease, Pancreatic