title: Prognostic value of partial genetic instability in neuroblastoma with ≤50% neuroblastic cell content.
abstract: OBJECTIVE
  Better understanding of neuroblastoma genetics will improve with genome-wide techniques. However, performing these analyses in samples with <60% neuroblast cells is not adequate. We evaluated the utility of fluorescence in situ hybridization (FISH) on tissue microarrays (TMA) in detecting partial genetic instability (PGI), focusing on samples with ≤50% neuroblast cells.
  
  
  RESULTS
  Alterations of 11q and 17q were detected by FISH on 369 neuroblastoma samples in TMA. Status of the MYCN gene and 1p36 region has been established previously by FISH diagnosis. Partial genetic instability (PGI) was defined as the ratio between segmental genetic alterations detected and number of genetic markers diagnosed in each tumour. Of primary tumours, 14.6% harboured 11q deletions, whereas 42.6% showed 17q gain. PGI was established in 260 primary tumours, 67 of which contained ≤50% neuroblasts. Outcomes were statistically worse for patients whose tumours presented high PGI (P < 0.0001). Multivariate analysis revealed moderate and high PGI as prognostic factors.
  
  
  CONCLUSIONS
  In the cohort examined in this study, univariate and multivariate analysis confirmed the effect of PGI in patient outcome. PGI established by FISH on TMA is a useful method to identify high-risk patients even if tumours have a cell content of ≤50% neuroblast cells.
authors.affiliation: Department of Pathology, Medical School, University of Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Piqueras
authors.forename: Samuel
authors.initials: S
authors.lastname: Navarro
authors.forename: Adela
authors.initials: A
authors.lastname: Cañete
authors.forename: Victoria
authors.initials: V
authors.lastname: Castel
authors.forename: Rosa
authors.initials: R
authors.lastname: Noguera
mesh_terms: D000293:Adolescent; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005819:Genetic Markers; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins