MYCN expression is not prognostic of adverse outcome in advanced-stage neuroblastoma with nonamplified MYCN.
OBJECTIVE
The clinical significance of MYCN expression in children with neuroblastoma (NB) remains controversial. To determine the prognostic significance of MYCN expression in the absence of MYCN amplification, we analyzed MYCN mRNA and protein expression in tumors from 69 patients.


METHODS
Sixty-nine NB tumor samples with nonamplified MYCN from patients with stage C or D disease were obtained from the Pediatric Oncology Group Neuroblastoma Tumor Bank. MYCN mRNA was analyzed using a real-time reverse transcriptase polymerase chain reaction assay, and MYCN protein was examined by Western blot analyses.


RESULTS
The estimated 5-year event-free survival (EFS) and survival (S) rates plus SE for the cohort were 57% +/- 17% and 60% +/- 16%, respectively. Infants younger than 1 year had significantly higher rates of EFS and S than children >/= 1 year of age (P =.003 and P <.001, respectively); patients with stage C disease had better outcome than those with stage D NB (P <.001); and patients with hyperdiploid tumors had better outcome than those with diploid NB (P <.001). Surprisingly, outcome was slightly better for patients with high versus low levels of MYCN mRNA expression (4-year S, 70% +/- 13% v 50% +/- 16%; P =.290), and for patients with tumors that expressed MYCN protein (4-year S, 73% +/- 19% v 53% +/- 15%, respectively; P =.171).


CONCLUSIONS
High levels of MYCN expression are not prognostic of adverse outcome in patients with advanced-stage NB with nonamplified MYCN. A trend associating high levels of MYCN expression with improved outcome was observed.
Cohn
S L
SL
Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA. scohn@northwestern.edu
London
W B
WB
Huang
D
D
Katzenstein
H M
HM
Salwen
H R
HR
Reinhart
T
T
Madafiglio
J
J
Marshall
G M
GM
Norris
M D
MD
Haber
M
M
D015153:Blotting, Western; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger