title: HIF-1α up-regulation is associated with adverse clinicopathological and biological factors in neuroblastomas.
abstract: OBJECTIVE
  To study the expression of hypoxia-inducible factor 1α (HIF-1α) in clinical neuroblastoma (NB) samples and its association with the clinicopathological features, biological features and survival of NB patients.
  
  
  RESULTS
  Immunohistochemistry indicated that elevated HIF-1α expression was present in 30 of 90 (33%) NBs. This expression was correlated significantly and positively with higher clinical stage (P = 0.002), ≥18 months of age at presentation (P = 0.020), high-risk group (P = 0.005), unfavourable pathology (P = 0.002), MYCN amplification (P < 0.001), 1p deletion (P = 0.004) and 17q gain (P = 0.002). Enzyme-linked immunosorbent assays showed that total HIF-1α protein was significantly higher in NBs of patients with all examined adverse prognostic factors except for age. Univariate survival analysis revealed that higher-than-median HIF-1α total protein levels were associated significantly with a decrease in event-free survival (EFS) (P = 0.017), but not in overall survival (OS) (P = 0.12). HIF-1α immunoexpression by ≥10% of tumour cells was associated significantly with decreased OS and EFS (P = 0.002 and P = 0.004, respectively), but not in multivariate analysis after adjusting for the high-risk group (P = 0.16 and P = 0.19, respectively).
  
  
  CONCLUSIONS
  HIF-1α was increased significantly in patients with NB associated with unfavourable characteristics. HIF-1α is a prognostic indicator of poor OS and EFS and defines subgroups of NBs with aggressive clinical behaviour.
authors.affiliation: Department of Histopathology, Bristol Royal Infirmary, Bristol, UK.
authors.forename: Josiah V
authors.initials: JV
authors.lastname: Dungwa
authors.forename: Linda P
authors.initials: LP
authors.lastname: Hunt
authors.forename: Pramila
authors.initials: P
authors.lastname: Ramani
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit