LACK OF CORRELATION OF N-MYC GENE AMPLIFICATION WITH PROGNOSIS IN LOCALIZED NEUROBLASTOMA - A PEDIATRIC-ONCOLOGY-GROUP STUDY

Multiple copies of N-myc proto-oncogene are only rarely detected in lo calized neuroblastomas (NBs), and the prognostic relevance of amplific ation in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biolog y Study and identified six patients with localized NBs harboring N-myc gene amplification. Three patients whose tumors showed favorable hist ology by Shimada classification and low-risk histological features acc ording to the Joshi classification have remained disease-free, whereas two of three patients with unfavorable histology tumors have develope d recurrent disease. Although earlier studies have indicated that N-my c amplification is associated with diploid DNA content, flow cytometri c analysis revealed that only two of the localized tumors contained st em lines with diploid DNA content. Loss of chromosome 1p was not detec ted by fluorescence in situ hybridization in the two tumors examined. N-myc protein was detected by immunohistochemical studies in four of t he five NBs analyzed. However, N-myc protein was not visualized in one of the tumors with stroma-rich histology, and Western blot analysis r evealed only low levels of N-myc protein expression in another NB with favorable histology. These studies indicate that the presence of N-my c amplification in localized NBs does not necessarily portend an adver se outcome. Furthermore, the biological features of this subset of N-m yc-amplified NBs appear to differ from those of more advanced N-myc-am plified tumors.