Analysis of DNA ploidy and proliferative activity in relation to histology and N-myc amplification in neuroblastoma

Diploid DNA content, advanced stage, unfavorable histology, and N-myc amplification are all associated with aggressive disease and poor prognosis in childhood neuroblastoma. DNA diploidy is associated with advanced stage and unfavorable histology, but the relationships among ploidy, N-myc amplification, and proliferative activity are not known. To determine if DNA diploidy is associated with N-myc amplification, we studied 29 neuroblastomas with flow cytometric analysis and Southern blot analysis. Clinical and histologic features were also evaluated. Sixty percent of the N-myc-amplified tumors were diploid, compared to 26% of the neuroblastomas, which lacked N-myc amplification (P = 0.11). In our analysis of proliferative activity and N-myc amplification, a higher mean percentage of cells in S phase was seen in the N-myc-amplified tumors (13.4%) than in the unamplified tumors (10%), but again the result was not statistically significant (P = 0.14). Significant associations were seen between unfavorable histology and DNA diploidy (P = 0.05), and between unfavorable histology and high proliferative activity (P = 0.007). Our data suggest that biologic factors other than N-myc amplification play a role in determining the aggressiveness of at least some diploid neuroblastomas.