Prognostic significance of DNA di-tetraploidy in neuroblastoma.
BACKGROUND
Identification of biological factors may provide tools to discriminate poor risk neuroblastoma patients of diagnosis, to ultimately offer risk adapted treatment intensity.


METHODS
Tumour cell DNA content, MYCN amplification (NMA), deletion of the short arm of chromosome 1 (del 1p) as well as three serological markers were assessed in 179 children with neuroblastoma.


RESULTS
Localised regional disease (stage 1 to 3) was diagnosed in 98 patients, and disseminated disease in 81 patients (65 with stage 4, 16 with stage 4s). Median age at diagnosis was 12 months and the median observation time 4 years. Sixty-seven of 179 patients had near di-tetraploid tumours (37%), with a significantly worse prognosis of 44% overall survival at 4 years in comparison with 88% in near triploid tumours (P < .001). The near di-tetraploid group showed a significant correlation with additional adverse biological factors (NMA, del 1p: P < 0.001), age over 1 year (P< 0.001), clinical stage 4 (P< 0.001), elevated ferritin (P = 0.023), and elevated LDH (P< 0.001). Multivariate analysis based on the overall (OS) and event free survival (EFS) estimations revealed that near di-tetraploidy was the most powerful biological factor, with a P-value of <0.001 for EFS and OS, followed by NMA (P = 0.015) for OS and del 1p (P= 0.047) for EFS.


CONCLUSIONS
This analysis underlines the important influence of near di-tetraploidy on prognosis, and suggests that more efforts should be undertaken to implement this factor in future studies.
Ladenstein
R
R
Department of Paediatric Haemato-Oncology, St. Anna Children's Hospital, Vienna, Austria. ladenstein@ccri.univie.ac.at
Ambros
I M
IM
Pötschger
U
U
Amann
G
G
Urban
C
C
Fink
F M
FM
Schmitt
K
K
Jones
R
R
Slociak
M
M
Schilling
F
F
Ritter
J
J
Berthold
F
F
Gadner
H
H
Ambros
P F
PF
D000293:Adolescent; D000782:Aneuploidy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001317:Austria / Q000453:epidemiology; D014408:Biomarkers, Tumor / Q000097:blood; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D016259:Genes, myc; D005858:Germany / Q000453:epidemiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D015993:Life Tables; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D011044:Poland / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012306:Risk; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm