Unfavorable DNA ploidy and Ha-ras p21 findings in neuroblastomas detected through mass screening

Cancer. 1995 Aug 15;76(4):695-9. doi: 10.1002/1097-0142(19950815)76:4<695::aid-cncr2820760425>3.0.co;2-o.

Abstract

Background: Urinary mass screening has been available for 6-month-old infants throughout Japan since 1985. It is still controversial as to whether the program contributes to the detection of unfavorable neuroblastomas destined to present clinically when a patient reaches an older age. DNA diploidy and tetraploidy, low expression of Ha-ras p21, and an amplified N-myc gene status relate to an unfavorable prognosis. The authors examined these biologic indicators in neuroblastomas detected by urinary mass screening.

Patients and methods: Seventy-eight neuroblastomas detected by mass screening were studied for DNA ploidy using DNA flow cytometry, Ha-ras p21 expression using immunostaining, and N-myc gene copy number using slot-blot or Southern blot hybridization methods.

Results: Of 73 tumors with analyzable DNA flow cytometric results, 18 (24.7%) had diploidy (n = 7) or tetraploidy (n = 11). Twenty-eight (40.0%) of 70 tumors examined showed low-to-absent expression of Ha-ras p21. DNA diploid and tetraploid status correlated significantly with the low-to-absent expression of Ha-ras p21 (P = 0.00021). Fourteen (20.0%) of the 70 patients had both of these two unfavorable prognostic markers. N-myc amplification was not detected in 41 of 41 tumors studied. All 78 patients were alive 8-92 months after completion of treatment.

Conclusions: At least 20.0% of neuroblastomas detected by mass screening have unfavorable biologic prognostic markers. These patients may benefit from early detection and immediate treatment. However, the biologic features associated with a poor prognosis are not predictive of poor outcome in individual patients, and, therefore, should not be used to justify more intensive therapies.

MeSH terms

  • Aneuploidy
  • Chromosome Aberrations / diagnosis
  • Chromosome Aberrations / genetics
  • Chromosome Disorders
  • DNA, Neoplasm / genetics*
  • Flow Cytometry
  • Gene Amplification
  • Genes, myc
  • Humans
  • Infant
  • Japan
  • Mass Screening
  • Neuroblastoma / diagnosis
  • Neuroblastoma / genetics*
  • Neuroblastoma / prevention & control
  • Neuroblastoma / urine
  • Ploidies
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / metabolism*

Substances

  • DNA, Neoplasm
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)