Combined determination of n–myc oncogene amplification and dna ploidy in neuroblastoma complementary prognostic indicators

Abstract

Background. N‐myc gene amplification is a well‐established prognostic indicator in neuroblastoma. Flow cytometric analysis of nuclear DNA content has shown that an abnormal nuclear DNA content in neuroblastoma is associated with a better prognosis. Because some patients with N‐myc unamplified tumors have a poor prognosis, factors other than N‐myc amplification may play a role in determining the clinical behavior of neuroblastoma. In the current study, the authors correlated N‐myc gene amplification and flow cytometric nuclear DNA content with respect to prognosis. Methods. Forty‐one patients with neuroblastoma, including 15 screened patients, served as subjects. The copy number of the N‐myc gene was determined by Southern blot analysis. DNA ploidy analysis was done on nuclei isolated from formalin‐fixed, paraffin‐embedded blocks. Results. Of 40 specimens of neuroblastoma, 7 involved tumors containing amplification of the N‐myc gene and 33 did not; 13 specimens showed DNA diploidy, and 27 showed DNA aneuploidy (including 4 with DNA tetraploidy). The Kaplan‐Meier survival analysis indicated a significantly better prognosis in patients with unamplified N‐myc tumors compared with those with N‐myc amplified tumors (87.3% versus 28.6%, P <0.05) and in patients with DNA aneuploid tumors compared with those with DNA diploid tumors (96.3% versus 43.0%, P < 0.001). The difference in the survival of the two extreme combinations, (e.g., 25 with N‐myc unamplified and DNA aneuploidy [4 tetraploidy] versus 5 with N‐myc amplified and DNA diploidy) was more significant (96.0% versus 20.0%, P < 0.001) than any other combination. Conclusion. Evaluations of N‐myc gene amplification and DNA ploidy are complementary, and the combined determination of these two factors may be one of the most powerful prognostic indicators in neuroblastoma. Copyright © 1993 American Cancer Society