CORRELATION BETWEEN MORPHOLOGIC AND OTHER PROGNOSTIC MARKERS OF NEUROBLASTOMA - A STUDY OF HISTOLOGIC GRADE, DNA INDEX, N-MYC GENE COPY NUMBER, AND LACTIC-DEHYDROGENASE IN PATIENTS IN THE PEDIATRIC ONCOLOGY GROUP

Background. Histologic grades (HG), N-myc (NM) gene copy number, DNA i ndex (DI), and serum lactic dehydrogenase ( LDH) have been shown to be related to prognosis in neuroblastoma. The relationship between HG an d nonmorphologic prognostic markers has not been investigated previous ly. Methods. Each prognostic marker was determined independently and w ithout the knowledge of clinical features and outcome by different inv estigators in 275 (HG), 96 of 275 (DI), 94 of 275 (NM), and 224 of 275 patients (LDH) with neuroblastoma by methods described previously. Pa tients younger than 2 years of age were included in the analysis for D I. Patients of all ages were included in the analysis of HG, NM, and L DH. Results. A statistically significant association of low HG (i and 2) was found with DI of more than 1 (hyperdiploid), single copy of NM gene per haploid genome, and an LDH of less than 1500 IU/l (P value fo r each, < 0.001), factors that are associated with better prognosis. H igh HG was associated with DI of 1 (diploidy), amplified NM gene, and an LDH of 1500 or more, factors that are associated with aggressive be havior. Conclusion. The value of HG is strengthened by its statistical ly significant association with features that reflect tumor cell biolo gy of neuroblastoma. In view of the tissue sample size required for de termination of HG, consideration should be given to obtaining such a s ample in as many patients as is feasible if there is no contraindicati on to surgery. Nonmorphologic prognostic markers, when used in concert with HG, would provide a basis for individualized risk-specific thera py of this disease.