Analysis of N-myc amplification in relation to disease stage and histologic types in human neuroblastomas

Abstract

Both untreated and treated primary neuroblastomas from 52 patients were analyzed to determine the correlation between the amplification of N-myc oncogene and various prognostic factors. Amplification of N-myc was observed in eight of 28 untreated cases and in 12 of 24 treated cases. As a whole, 12 of 18 tumors (67%) in Stage IV had N-myc amplification, but there were fewer cases in the unadvanced disease stage, as reported previously by others. Furthermore, the authors detected N-myc amplification in three of nine tumors in Stage IV-S, although the amplification was less than 50 copies. Analysis of progression-free survival at 24 months revealed that amplification of N-myc was associated with the worst prognosis (P less than 0.001). In the untreated group, no amplification of N-myc was detected in any of two ganglioneuromas and four ganglioneuroblastomas, whereas amplification of N-myc was observed in all two round-cell and six of 20 rosette fibrillary neuroblastomas. On the other hand, the authors detected amplification of N-myc in three of eight less differentiated ganglioneuroblastomas in the treated group and observed the worst prognosis in these three patients. The total percentage of the cases from both untreated and treated groups suggest that amplification of N-myc may occur more frequently in undifferentiated types of neuroblastomas than in less malignant types. In conclusion, the amplification of N-myc in neuroblastomas was closely associated with the worst prognosis, which was suggested by both disease stage and histologic characteristics.

The p16 (CDKN2A) gene is involved in the growth of neuroblastoma cells and its expression is associated with prognosis of neuroblastoma patients

“…Twenty-two of 45 patients (49%) lacking p16 expression died within 5 years, whereas only two of 29 patients (7%) with p16 expression died within this period (Figure 4). Although age and N-myc ampli®cation have been known as signi®cant prognostic factors in neuroblastoma (Tsuda et al, 1987;Tonini, 1993), loss of p16 expression was not correlated with age and N-myc ampli®cation.…”

MYC oncogenes and human neoplastic disease

“…These original ®ndings have generally been con®rmed in subsequent studies (Combaret et al, 1996;Rubie et al, 1997;Tsuda et al, 1997). Overall, N-MYC ampli®cation remains the most widely accepted predictive parameter of long-term, disease-free survival.…”

Overexpression of multiple oncogenes related to histological grade of astrocytic glioma

“…Studies of over 800 patients with neuroblastoma (Bertram & Berthold, 1987;Nakagarawa et al, 1987;Tsuda et al, 1987, and see Brodeur, 1990 for review), a tumour of primitive neuronal cells which occurs predominantly outside the brain, have shown that amplification of the N-myc oncogene is associated with rapid progression and poor prognosis. Another oncogene which may serve as a marker of prognosis is c-erbB-2 (or HER-2 or neu).…”