Different genomic and metabolic patterns between mass screening-positive and mass screening-negative later-presenting neuroblastomas.
The mass screening of neuroblastoma has been undertaken in Japan by measuring urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) in all infants at the age of 6 months. This program may not only improve the prognosis but also provide important insights into the biology and evolution of human neuroblastoma. The authors studied and discuss the clinical significance of the N-myc oncogene, catecholamine metabolism, and other tumor markers in 43 patients with neuroblastoma who underwent the urinary screening test at 6 months of age. Thirty patients were found by the screening, and 13 were negative at the screening but later had a tumor. In the former group, the tumors were mostly in early stages (Stage I, 12; Stage II, 11; Stage III, seven), no amplification of N-myc was observed, and all patients are alive without disease. Although two patients whose urine at the screening showed elevated VMA and HVA levels and accidentally were not treated for 13 and 17 months, there was no change in the values of VMA and HVA during that time. However, in the latter group, the tumors were mostly in advanced stages (Stage I, one; Stage III, four; Stage IV, eight) and N-myc amplification was observed in seven of 13. Only two of these 13 are alive without disease. The age at diagnosis of the screening-negative group was 23 months compared with 8 months in the patients identified by screening, and the pattern of catecholamine metabolites in the screening-negative group tended to be dopaminergic with a low VMA-HVA ratio, especially in cases with N-myc amplification. These data suggest that the screening-positive patients with neuroblastoma may have favorable characteristics, and the biology of these tumors may be different from that of screening-negative later-presenting tumors. They also suggest that there may be at least two distinct subsets of neuroblastoma. For the early detection of the poor prognostic neuroblastomas, the measurement of urinary dopamine with VMA and HVA at later ages, such as 1 to 2 years, should be considered.
Nakagawara
A
A
Department of Pediatric Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Zaizen
Y
Y
Ikeda
K
K
Suita
S
S
Ohgami
H
H
Nagahara
N
N
Sera
Y
Y
Akiyama
H
H
Kawakami
K
K
Uchino
J
J
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis*; D015139:Blotting, Southern; D002675:Child, Preschool; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005293:Ferritins / Q000097:blood; D005729:Ganglioneuroma / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics; D016678:Genome; D006719:Homovanillic Acid / Q000652:urine*; D006801:Humans; D007223:Infant; D007564:Japan; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008403:Mass Screening; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011954:Receptors, Dopamine / Q000032:analysis; D014642:Vanilmandelic Acid / Q000652:urine*
D014408:Biomarkers, Tumor; D015342:DNA Probes; D004273:DNA, Neoplasm; D011954:Receptors, Dopamine; D014642:Vanilmandelic Acid; D005293:Ferritins; D007770:L-Lactate Dehydrogenase; D010751:Phosphopyruvate Hydratase; D006719:Homovanillic Acid