Prognostic significance of MYCN oncogene expression in childhood neuroblastoma.
OBJECTIVE
To assess the significance of MYCN gene expression as a prognostic factor in patients with neuroblastoma of various ages, and to determine whether it can predict for outcome independently of MYCN gene amplification.


METHODS
The level of MYCN gene expression in 60 specimens of primary untreated neuroblastoma was determined by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis.


RESULTS
High levels of MYCN gene expression were associated with advanced tumor stage (P=.0005), with the presence of MYCN gene amplification (P < .0001), but not with older age at diagnosis. Among patients who lacked MYCN gene amplification, the levels of MYCN gene expression were significantly greater in the tumors of infants compared with those of older children (P < .0005). High MYCN expression was strongly associated with reduced survival and event-free survival in the overall study population (P < .005), and also in the subset of patients aged older than 1 year at diagnosis (P < .001). In contrast, MYCN expression did not appear to be predictive of outcome in infants. After adjustment for the effect of MYCN amplification, high levels of MYCN expression retained significant prognostic value for poor survival (relative hazards, 30.3; P=.003) in children aged older than 12 months at diagnosis.


CONCLUSIONS
High MYCN gene expression is strongly predictive of poor outcome in older children with neuroblastoma, but not in infants. The findings help explain the controversy in the literature about the prognostic value of MYCN gene expression and highlight the different biology of neuroblastoma that presents in infants and older children.
Children's Cancer Research Institute, Sydney Children's Hospital, Randwick, NSW, Australia.
S B
SB
Bordow
M D
MD
Norris
P S
PS
Haber
G M
GM
Marshall
M
M
Haber
D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005784:Gene Amplification; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate