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


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.
Kusafuka
T
T
Department of Pediatric Surgery, Osaka University Medical School, Suita, Japan.
Nagahara
N
N
Oue
T
T
Imura
K
K
Nakamura
T
T
Kobayashi
Y
Y
Komoto
Y
Y
Fukuzawa
M
M
Okada
A
A
Nakayama
M
M
D000782:Aneuploidy; D002869:Chromosome Aberrations / Q000175:diagnosis / Q000235:genetics; D025063:Chromosome Disorders; D004273:DNA, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007223:Infant; D007564:Japan; D008403:Mass Screening; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control / Q000652:urine; D011003:Ploidies; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*
D004273:DNA, Neoplasm; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)