Combined determination of N-myc oncogene amplification and DNA ploidy in neuroblastoma. Complementary prognostic indicators.
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.


CONCLUSIONS
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.
Muraji
T
T
Department of Surgery, Kobe Children's Hospital, Japan.
Okamoto
E
E
Fujimoto
J
J
Suita
S
S
Nakagawara
A
A
D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality* / Q000648:ultrastructure; D011003:Ploidies; D011379:Prognosis; D016019:Survival Analysis
D004273:DNA, Neoplasm