Journal of Clinical Oncology, Vol 16, 3286-3294, Copyright © 1998 by American Society of Clinical Oncology
Prognostic significance of MYCN oncogene expression in childhood neuroblastoma
SB Bordow, MD Norris, PS Haber, GM Marshall and M Haber
Children's Cancer Research Institute, Sydney Children's Hospital, Randwick, NSW, Australia.
PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
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