MYCN ONCOGENE AMPLIFICATION IN NEUROBLASTOMA IS ASSOCIATED WITH WORSEPROGNOSIS, EXCEPT IN STAGE-4S - THE ITALIAN EXPERIENCE WITH 295 CHILDREN

Purpose: To evaluate the prognostic role of MYCN oncogene amplificatio n in children with neuroblastoma. Patients and Methods: Of 694 childre n (age, 0 to 15 years) with previously untreated neuroblastoma, 295 (4 2%) were evaluated at diagnosis for MYCN gene amplification. Results: Clinical characteristics and survival results of 295 patients studied and 399 not studied for MYCN were comparable. In 48 of 295 patients st udied for MYCN (16%), the gene was amplified (greater than or equal to three gene copies). Amplification was more frequent in children older than 1 year, with abdominal tumor (18% v 7%), advanced disease, norma l vanillylmandelic (VMA) urinary excretion, and high lactate dehydroge nase (LDH), ferritin, and neuron-specific enolase (NSE) serum levels. In patients studied for MYCN, the 5-year overall survival (OS) rate wa s higher for children aged less than 1 year (90% v 44%), with extraabd ominal tumor, stage 1 or 2 versus 3 versus 4, and normal NSE, LDH, and ferritin serum levels. patients with amplified MYCN had a worse OS (o dds ratio [OR], 3.38; confidence interval [CI], 2.22 to 5.16). This as sociation held after adjustment for other characteristics. The impact of MYCN amplification was greater in patients with favorable character istics, in particular age (OR, 10.28 for infants; 2.08 for older child ren) and stage (OR, 35.3 for stage 1 to 2; 8.41 for stage 3; 1.76 for stage 4). However, of 29 children with stage 4s, all three with amplif ied MYCN survive. In a multivariate analysis, the prognostic role of M YCN amplification, age, and stage was confirmed, but the size of the e ffect of MYCN was dependent on age and stage. Conclusion: MYCN amplifi cation is associated with a worse prognosis in children with neuroblas toma at all ages and stages except 4s. This association is most pronou nced in children with otherwise favorable prognostic indicators, and i n these children should be considered as an indication for more intens ive intervention. (C) 1997 by American Society of Clinical Oncology.