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Lack of Correlation of N-myc Gene Amplification with Prognosis in Localized Neuroblastoma: A Pediatric Oncology Group Study¹

Departments of Pediatrics and Tumor Cell Biology, Northwestern University and Children's Memorial Hospital, Chicago, Illinois [S. L. C., H. S., D. C., L. C.]; Department of Experimental Oncology, St. Jude Children's Research Hospital and the Department of Pediatrics, University of Tennessee, Memphis, Tennessee [A. T. L., S. T. R., M. B. V., H. K., L. C. B.]; Departments of Pediatrics and Pathology, East Carolina University School of Medicine, Greenville, North Carolina [V. V. J., T. H.]; Department of Pediatrics, University of Alabama, Birmingham, Alabama [R. P. C.]; Department of Statistics, University of Florida and Pediatric Oncology Group Statistical Office, Gainesville, Florida [P. V. R.]; Department of Pediatrics, University of Southern California School of Medicine, Los Angeles, California [R. C. S.]; Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania [G. M. B.]

Multiple copies of N-myc proto-oncogene are only rarely detected in localized neuroblastomas (NBs), and the prognostic relevance of amplification in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biology Study and identified six patients with localized NBs harboring N-myc gene amplification. Three patients whose tumors showed favorable histology by Shimada classification and low-risk histological features according to the Joshi classification have remained disease-free, whereas two of three patients with unfavorable histology tumors have developed recurrent disease. Although earlier studies have indicated that N-myc amplification is associated with diploid DNA content, flow cytometric analysis revealed that only two of the localized tumors contained stem lines with diploid DNA content. Loss of chromosome 1p was not detected by fluorescence in situ hybridization in the two tumors examined. N-myc protein was detected by immunohistochemical studies in four of the five NBs analyzed. However, N-myc protein was not visualized in one of the tumors with stroma-rich histology, and Western blot analysis revealed only low levels of N-myc protein expression in another NB with favorable histology. These studies indicate that the presence of N-myc amplification in localized NBs does not necessarily portend an adverse outcome. Furthermore, the biological features of this subset of N-myc-amplified NBs appear to differ from those of more advanced N-myc-amplified tumors.

¹ This work was supported in part by the Elise Anderson Neuroblastoma Research Fund (S. L. C.), the Brian Fox Memorial Fund (S. L. C.), the Michael Sexton Memorial Fund (S. L. C.), The Terry Fox Run, cosponsored by the Ritz Carlton and Four Seasons Hotels, Chicago (S. L. C.), Grants CA-51061 (S. L. C.), CA-07431 (S. L. C.), CA-23099 (A. T. L.), CA-31566 (A. T. L.), CA-39771 (G. M. B.), CA-05887 (G. M. B.), CA-25408 (R. P. C.), CA-15515 (T. H.), CA-29139 (P. V. R.), Cancer Center Support (CORE) Grant CA-21765 (A. T. L.) from the National Cancer Institute, NIH, and the American Lebanese Syrian Associated Charities, St. Jude Children's Research Hospital (A. T. L.).

² To whom requests for reprints should be addressed, at Pediatric Oncology Group, 645 N. Michigan Ave., Suite 910, Chicago, IL 60611.

Received 9/19/94. Accepted 1/ 5/95.

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