Neuroblastoma, alone among extra-CNS childhood tumors, has been shown to express a unique proto-oncogene, N-myc. Further, elevated expression and/or amplification of this oncogene has been correlated with adverse clinical course; no stage I or II patients express the gene abnormally, while over 50% of stage III and IV patients do. Current work indicates these patients fare especially poorly. Nonetheless, no work to date has attempted to correlate the expression of N-myc by individual tumor cells with stage and outcome. Bulk techniques employed to date cannot distinguish a small population of N-myc expressor tumor cells admixed with non-expressors, yet such patients may prove to have a prognosis equally adverse as those with high levels of N-myc expression. This might be the case with the N- myc negative stage III and IV patients reported to date. The present study will examine N-myc expression as DNA copies, RNA transcripts and N-myc protein as detected by in situ hybridization with radiolabelled DNA fragments of the N-myc gene, transcribed in vitro and hybridized to frozen sections of approximately 80 tumors provided by one of us (RS). Likewise, N-myc protein will be detected immunocytochemically by antibodies specific for oligopeptide regions of the N-myc protein product. The incidence of positive tumor cells and their morphology will be assessed in each case, and upon completion of the study, the identity, stage, and status of each patient will be correlated with N-myc expression.
