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 index (DI), and serum lactic dehydrogenase (LDH) have been shown to be related to prognosis in neuroblastoma. The relationship between HG and nonmorphologic prognostic markers has not been investigated previously.

Methods: Each prognostic marker was determined independently and without the knowledge of clinical features and outcome by different investigators in 275 (HG), 96 of 275 (DI), 94 of 275 (NM), and 224 of 275 patients (LDH) with neuroblastoma by methods described previously. Patients younger than 2 years of age were included in the analysis for DI. Patients of all ages were included in the analysis of HG, NM, and LDH.

Results: A statistically significant association of low HG (1 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 for each, < 0.001), factors that are associated with better prognosis. High HG was associated with DI of 1 (diploidy), amplified NM gene, and an LDH of 1500 or more, factors that are associated with aggressive behavior.

Conclusion: The value of HG is strengthened by its statistically significant association with features that reflect tumor cell biology of neuroblastoma. In view of the tissue sample size required for determination of HG, consideration should be given to obtaining such a sample in as many patients as is feasible if there is no contraindication to surgery. Nonmorphologic prognostic markers, when used in concert with HG, would provide a basis for individualized risk-specific therapy of this disease.