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Combined Analysis of DNA Ploidy Index and N-myc Genomic Content in Neuroblastoma¹

Laboratory of Molecular and Clinical Pharmacology [J. B., G. R., J. B.] and Departments of Statistics (U Inserm No. 147) [F. D. V.], Pediatrics [O. H., J. L.], and Pathology [M. J. T-L.], Institut Gustave Roussy, rue Camille Desmoulins, 94800 Villejuif cedex, France; Gray Laboratory of the Cancer Research Campaign, Mount Vernon Hospital, HA62RN Northwood, Middlesex, [G. D. W., N. J. M.], United Kingdom; and Department of Pathology, Hôpital Trousseau, Paris, [L. B-G.] France

The aim of the study was to assess, in a group of nonselected patients with neuroblastoma, the prognostic value of both N-myc gene amplification and DNA ploidy index, taking into account potential confounding factors such as age and stage. Of 59 patients studied, 23 were younger than 1 year at diagnosis, 31 presented with stage IV, 10 with stage III, 5 with stage II, 8 with stage I, and 4 with stage IV-S. N-myc genomic content was analyzed by Southern blot hybridization technique and N-myc amplification (3 copies/haploid genome) was present in 6 stage IV, 2 stage III, and 1 stage IV-S. The DNA ploidy index was analyzed by flow cytometry. Of the 59 neuroblastomas, 26 were diploid (DNA index, 1) and 33 were aneuploid (DNA index, >1). The majority of the aneuploid tumors (28 of 33) were near-triploid with DNA indexes between 1.25 and 1.68, 4 were near-diploid (DNA index up to 1.18), and 1 was hypotetraploid (DNA index, 1.85). The proportion of near-triploid tumors was significantly greater among patients under 1 year of age and among patients presenting with stages I, II, and IV-S. Interestingly, 0 of 28 near-triploid neuroblastomas exhibited N-myc gene amplification, compared to 9 of 31 in the group of diploid, near-diploid, and hypotetraploid tumors (Fisher's exact test, P < 0.001).

Four factors were significantly related to a high risk of relapse in univariate analysis, i.e., age, stage, DNA index, and N-myc amplification. In multivariate analysis, only N-myc amplification and the DNA index remained significantly associated with a high risk of relapse. The 2-year disease-free survival rate was 94% (95% confidence interval, 77–98%) for patients with near-triploid neuroblastoma, compared to 45 and 11% (95% confidence interval, 32–70 and 4–23%) for patients with diploid or near-diploid tumors, without and with N-myc amplification, respectively. We concluded that the combination of N-myc and DNA index should be included in routine management of neuroblastoma.

¹ This work was supported by Institut Gustave Roussy, Contrat de Recherche Clinique, 88CD9.

² Recipient of a fellowship from the Association de la Recherche sur le Cancer, ARC.

³ To whom requests for reprints should be addressed.

Received 7/30/90. Accepted 10/ 4/90.

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