title: Detection of N-myc amplification by FISH in immature areas of fixed neuroblastomas: more efficient than Southern blot/PCR.
abstract: N-myc amplification is a major prognostic factor in neuroblastomas and is systematically investigated by Southern blot or polymerase chain reaction (PCR). A retrospective study of N -myc amplification has been carried out using fluorescence in situ hybridization (FISH) in 97 fixed neuroblastomas. For each tumour, FISH was performed on the area that contained the most immature neuroblasts. Among these 97 neuroblastomas, 16 were amplified and 12 were not interpretable. FISH was not interpretable in six cases. All neuroblastomas with N-myc amplification detected by Southern blot/PCR were amplified with FISH, except three that were not interpretable. Four tumours that were not interpretable in Southern blot/PCR contained more than five copies of N-myc by FISH: one was aneuploid and three were truly amplified, containing more than ten copies of N-myc. Among these three patients, two died in a short time of their tumours. Ten cases were not amplified by Southern blot/PCR and showed more than five copies by FISH: four were aneuploid and two showed heterogeneous amplification, with a few cells clearly amplified whereas most were not. Four cases were amplified, of which two patients died of their tumours. This study confirms that when applied to the most immature areas of fixed neuroblastomas, FISH displayed a higher sensitivity than molecular techniques (p < 0.001) and could detect heterogeneous amplification. FISH could therefore become an important complementary procedure in assessing prognosis in neuroblastomas.
authors.affiliation: Department of Pathology, CHU de Grenoble, 38043 Grenoble Cedex 09, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Sartelet
authors.forename: Laurence
authors.initials: L
authors.lastname: Grossi
authors.forename: Dominique
authors.initials: D
authors.lastname: Pasquier
authors.forename: Valérie
authors.initials: V
authors.lastname: Combaret
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bouvier
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchère
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Martine
authors.initials: M
authors.lastname: Munzer
authors.forename: Thierry
authors.initials: T
authors.lastname: Philip
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Zahm
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.forename: Dominique
authors.initials: D
authors.lastname: Gaillard
authors.forename: Basile
authors.initials: B
authors.lastname: Pasquier
mesh_terms: D015139:Blotting, Southern / Q000379:methods; D002675:Child, Preschool; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity