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Previous Volume 334:225-230 January 25, 1996 Number 4 Next

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ABSTRACT

Background Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic value.

Methods We used Southern blot analysis to study the allelic loss of chromosomes 1p, 4p, 11q, and 14q, the duplication of chromosome 17q, and the amplification of the N-myc oncogene in 89 neuroblastomas. We also determined the nuclear DNA content of the tumor cells.

Results Allelic loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q were significantly associated with unfavorable outcomes. In a multivariate analysis, loss of chromosome 1p was the most powerful prognostic factor. It provided strong prognostic information when it was included in multivariate models containing the prognostic factors of age and stage or serum ferritin level and stage. Among the patients with stage I, II, or IVS disease, the mean (±SD) three-year event-free survival was 100 percent in those without allelic loss of chromosome 1p and 34±15 percent in those with such loss; the rates of three-year event-free survival among the patients with stage III and stage IV disease were 53±10 percent and 0 percent, respectively.

Conclusions The loss of chromosome 1p is a strong prognostic factor in patients with neuroblastoma, independently of age and stage. It reliably identifies patients at high risk in stages I, II, and IVS, which are otherwise clinically favorable. More intensive therapy may be considered in these patients. Patients in stages III and IV with allelic loss of chromosome 1p have a very poor outlook, whereas those without such loss are at moderate risk.

Source Information

From the Department of Pediatric Oncology and Hematology, Emma Kinderziekenhuis–Academic Medical Center (H.C., J.K., P.A.V.), and the Institute of Human Genetics, Academic Medical Center (H.C., P.S., R.S., A.W., R.V.), University of Amsterdam, Amsterdam; the Center of Pediatric Oncology of the Southeastern Netherlands, University of Nijmegen, Nijmegen (J.B.); and the Sophia Kinderziekenhuis, Erasmus University, Rotterdam (M.E.) — all in the Netherlands; and the Institute of Human Genetics, University Hospital of Ghent, Ghent, Belgium (G.L.).

Address reprint requests to Dr. Caron at the Department of Pediatric Oncology and Hematology, EKZ/AMC, P.O. Box 22700, 1100 DE Amsterdam, the Netherlands.

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