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 w hether the program contributes to the detection of unfavorable neurobl astomas 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 neurob lastomas 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 me thods. Results. Of 73 tumors with analyzable DNA flow cytometric resul ts, 18 (24.7%) had diploidy (n = 7) or tetraploidy (n = 11). Twenty-ei ght (40.0%) of 70 tumors examined showed low-to-absent expression of H a-ras p21. DNA diploid and tetraploid status correlated significantly with the low-to-absent expression of Ha-ras p21 (P = 0.00021). Fourtee n (20.0%) of the 70 patients had both of these two unfavorable prognos tic markers. N-myc amplification was not detected in 41 of 41 tumors s tudied. All 78 patients were alive 8-92 months after completion of tre atment. Conclusions. At least 20.0% of neuroblastomas detected by mass screening have unfavorable biologic prognostic markers. These patient s may benefit from early detection and immediate treatment. However, t he biologic features associated with a poor prognosis are not predicti ve of poor outcome in individual patients, and, therefore, should not be used to justify more intensive therapies.