title: DNA content heterogeneity in neuroblastoma analyzed by means of image cytometry and its potential significance.
abstract: The aim of this study was to determine the frequency and significance of the tumor DNA content heterogeneity in 33 previously untreated human neuroblastomas. We used image cytometry to selectively analyze neuroblasts by excluding karyorrhectic or stromal cells from cytometric measurements. DNA content heterogeneity with more than one clonal subpopulation on DNA histogram was found in 8 of 33 cases. Of these 8 cases, 4 showed MYCN amplification. Double labeling fluorescent in situ hybridization with probes for the centromeric region of chromosome 2 and MYCN gene was used to confirm the DNA content heterogeneity. DNA content heterogeneity was associated with poorer prognosis in this study (P<0.05). There was a significant correlation between euploidy (di- and tetraploidy) and worse prognosis, but only when heterogeneous neuroblastomas with euploid cell population were assigned to euploid tumors (P=0.006). Our results may explain the conflicting data in the literature regarding ploidy and suggest that DNA content heterogeneity and the presence of a euploid population may predict worse prognosis in neuroblastoma patients.
authors.affiliation: Department of Molecular Pathology, National Institute of Oncology, Budapest, Hungary. eghbor@excite.com
authors.forename: Zsombor
authors.initials: Z
authors.lastname: Melegh
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Csernák
authors.forename: Erika
authors.initials: E
authors.lastname: Tóth
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Veleczki
authors.forename: Edina
authors.initials: E
authors.lastname: Magyarosy
authors.forename: Kálmán
authors.initials: K
authors.lastname: Nagy
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szentirmay
mesh_terms: D000782:Aneuploidy; D002467:Cell Nucleus / Q000737:chemistry; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D019044:Image Cytometry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011003:Ploidies; D011379:Prognosis; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins