Prognostic discrimination among neuroblastomas according to Ha-ras/trk A gene expression: a comparison of the profiles of neuroblastomas detected clinically and those detected through mass screening.
BACKGROUND
Neuroblastomas (NBs) exhibit a wide variety of clinical behavior. It is important to determine the biology of NB before treatment is instituted.


METHODS
One hundred six NBs detected clinically (clinical NBs) were classified according to immunohistochemical expression of the Ha-ras and trk A genes. Association of the two-gene expression with patient outcome was examined retrospectively, and the possibility of prognostic prediction was evaluated. The profile of the expression of the two genes in 85 NBs detected through mass screening (mass NBs) was compared with that in clinical NBs.


RESULTS
Ha-rasltrk A expression in clinical NBs was associated with disease free survival, even when the NBs had no amplification of the N-myc gene. Multivariate analysis demonstrated that the expression of Ha-rasl/trk A was a significant prognostic factor that was independent of stage, age at diagnosis, and N-myc amplification. Favorable outcomes of patients with advanced NB were distinguished by high Ha-ras and high trk A expression, and unfavorable outcomes were distinguished by low Ha-ras and low trk A expression. A profile of the two genes in mass NBs was different from that in clinical NBs. Greater than 50% of the mass NBs were detected as localized tumors with high Ha-ras and high trk A expression. The mass screening detected NBs with favorable and unfavorable biology.


CONCLUSIONS
The expression of Ha-ras and trk A is an excellent predictor of both favorable and unfavorable biology in NBs. The information it provides can be important in determining the appropriate therapeutic intervention for each patient.
Department of Pediatrics, National Kure Hospital, Hiroshima, Japan.
T
T
Tanaka
T
T
Sugimoto
T
T
Sawada
D000367:Age Factors; D001695:Biology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005544:Forecasting; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008403:Mass Screening; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009857:Oncogenes / Q000235:genetics*; D010347:Patient Care Planning; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D012189:Retrospective Studies
D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA