Current urinary mass screening for catecholamine metabolites at 6 months of age may be detecting only a small portion of high-risk neuroblastomas: a chromosome and N-myc amplification study.

Abstract

We studied 96 infants and children with untreated neuroblastomas. Chromosomes of tumor cells were analyzed in 68, and N-myc copy numbers were determined in 67 patients. Patients found by a mass screening program for 6-month-old infants (group A1, 39 patients) or those less than 12 months of age found clinically (group A2, 13 patients) were rarely in the disseminated stage (A1, three of 39; A2 one of 13); their tumors usually had near-triploid (3n) or hypertetraploid (greater than 4n) karyotypes (A1, 28 of 37; A2, nine of 11), and never had N-myc amplification (A1, zero of 34; A2, zero of 11). In contrast, children 12 months or over (group B, 27 patients) were usually in the disseminated stage (19 of 27) (P less than .0001); their tumors usually had near-diploid (2n) or near-tetraploid (4n) karyotypes (16 of 20) (P = .0027), and often had N-myc amplification (nine of 22) (P less than .0001). Of the 40 clinically found patients (A2 and B), six had undergone the screening with a negative result at the age of 6 months. Two of the six patients had N-myc amplification in the tumors. Most tumors found by the screening showed known characteristics predicting a good prognosis, and the majority of tumors showing characteristics predicting a poor prognosis were found in patients aged between 12 and 36 months. Our chromosome and N-myc amplification studies suggest that a low-risk tumor does not usually evolve to a high-risk tumor. Thus, the current mass screening program may be detecting only a small portion of highly malignant neuroblastomas at the earliest stage. Infants should be screened twice, at 6 months as well as at 12 months of age, for the early detection of high-risk neuroblastomas.

Effects of mass screening on age-specific incidence of neuroblastoma

“…Even during infancy, only 36% of infants with neuroblastoma in Stage 111 or IV survive (Sawaguchi et al, 1979). Besides prognosis, neuroblastomas found by screening have many features that differ from those of clinically detected tumors and the majority of neuroblastomas detected by screening have features which are prognostically favorable (Hayashi et al, 1988;Kaneko et al, 1990).…”

Fluorescence in situ hybridization combined with immunohistochemistry for highly sensitive detection of chromosome 1 aberrations in neuroblastoma

“…More recent studies (Kaneko et al, 1990;Fong et al, 1992) show that 1 p abnormalities lose prognostic significance after patients are stratified for MYCN amplification. However, more detailed investigations are required to elucidate the exact prognostic sig nificance of lp deletions in neuroblastoma.…”

Neuroblastoma screening in infants postponed after the sixth month of age: A trial to reduce “overdiagnosis” and to detect cases with “unfavorable” biologic features

“…At that time, however, the first critical reports about neuroblastoma screening were published [14][15][16][17][18][19][20]. These reports emphasized the ''overdiagnosis'' of neuroblastoma cases by early screening, and some authors argued that neuroblastoma screening at an age of 6 months might predominantly detect neuroblastomas that would never be diagnosed clinically, i.e., tumors that would regress spontaneously [18,[20][21][22].…”

“…In fact, the introduction of early neuroblastoma screening has led to an overdiagnosis of this disease and neuroblastoma incidence has doubled in screening areas [22][23][24][25][26][27]. Analysis of the biologic features of neuroblastomas detected by the Japanese screening programs and those presenting clinically showed remarkably differing findings [15,19,[28][29][30][31][32][33]. In addition, children developing neuroblastoma after the 6-months test were frequently missed by early screening [14,15,18,19].…”