Abstract
The association between tumour N-myc amplification, DNA ploidy, and various prognostic factors (patient age, tumour stage at diagnosis, primary site and histopathological differentiation) was studied in 18 children who had neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. Amplification of genomic N-myc was observed in six patients who had been treated with chemotherapy before surgery (one with stage III and five with stage IV). All these tumours were located in the adrenal or upper retroperitoneum; five were neuroblastomas and one was a ganglioneuroblastoma. Three of them were aneuploid and three diploid. The degree of N-myc patients with tumour N-amplification varied from 20 to 1500 copies without relation to ploidy. All patients with tumour N-myc amplification died of their tumour. Amplification was always associated with poor prognosis, independent of tumour cell ploidy. Four patients without such amplification also died: three had diploid tumours, the fourth was aneuploid. It is suggested that genomic N-myc amplification takes place mainly in adrenal and retroperitoneal neuroblastomas and can be a feature of tumours with and without histological signs of differentiation. The precise role of N-myc in the pathogenesis of neuroblastoma remains unclear.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allan P. M., Garson J. A., Harper E. I., Asser U., Coakham H. B., Brownell B., Kemshead J. T. Biological characterization and clinical applications of a monoclonal antibody recognizing an antigen restricted to neuroectodermal tissues. Int J Cancer. 1983 May 15;31(5):591–598. doi: 10.1002/ijc.2910310510. [DOI] [PubMed] [Google Scholar]
- Beckwith J. B., Martin R. F. Observations on the histopathology of neuroblastomas. J Pediatr Surg. 1968 Feb;3(1):106–110. doi: 10.1016/0022-3468(68)90989-5. [DOI] [PubMed] [Google Scholar]
- Brandtzaeg P., Rognum T. O. Evaluation of tissue preparation methods and paired immunofluorescence staining for immunocytochemistry of lymphomas. Histochem J. 1983 Jul;15(7):655–689. doi: 10.1007/BF01002987. [DOI] [PubMed] [Google Scholar]
- Brodeur G. M., Green A. A., Hayes F. A., Williams K. J., Williams D. L., Tsiatis A. A. Cytogenetic features of human neuroblastomas and cell lines. Cancer Res. 1981 Nov;41(11 Pt 1):4678–4686. [PubMed] [Google Scholar]
- Brodeur G. M., Hayes F. A., Green A. A., Casper J. T., Wasson J., Wallach S., Seeger R. C. Consistent N-myc copy number in simultaneous or consecutive neuroblastoma samples from sixty individual patients. Cancer Res. 1987 Aug 15;47(16):4248–4253. [PubMed] [Google Scholar]
- Evans A. E., Albo V., D'Angio G. J., Finklestein J. Z., Leiken S., Santulli T., Weiner J., Hammond G. D. Factors influencing survival of children with nonmetastatic neuroblastoma. Cancer. 1976 Aug;38(2):661–666. doi: 10.1002/1097-0142(197608)38:2<661::aid-cncr2820380206>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
- Evans A. E. Staging and treatment of neuroblastoma. Cancer. 1980 Apr 15;45(7 Suppl):1799–1802. [PubMed] [Google Scholar]
- Hedley D. W., Friedlander M. L., Taylor I. W., Rugg C. A., Musgrove E. A. Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem. 1983 Nov;31(11):1333–1335. doi: 10.1177/31.11.6619538. [DOI] [PubMed] [Google Scholar]
- Nakagawara A., Ikeda K., Tsuda T., Higashi K., Okabe T. Amplification of N-myc oncogene in stage II and IVS neuroblastomas may be a prognostic indicator. J Pediatr Surg. 1987 May;22(5):415–418. doi: 10.1016/s0022-3468(87)80260-9. [DOI] [PubMed] [Google Scholar]
- Oppedal B. R., Storm-Mathisen I., Lie S. O., Brandtzaeg P. Prognostic factors in neuroblastoma. Clinical, histopathologic, and immunohistochemical features and DNA ploidy in relation to prognosis. Cancer. 1988 Aug 15;62(4):772–780. doi: 10.1002/1097-0142(19880815)62:4<772::aid-cncr2820620422>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
- Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
- Schwab M., Varmus H. E., Bishop J. M., Grzeschik K. H., Naylor S. L., Sakaguchi A. Y., Brodeur G., Trent J. Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc. Nature. 1984 Mar 15;308(5956):288–291. doi: 10.1038/308288a0. [DOI] [PubMed] [Google Scholar]
- Seeger R. C., Brodeur G. M., Sather H., Dalton A., Siegel S. E., Wong K. Y., Hammond D. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985 Oct 31;313(18):1111–1116. doi: 10.1056/NEJM198510313131802. [DOI] [PubMed] [Google Scholar]
- Tsuda H., Shimosato Y., Upton M. P., Yokota J., Terada M., Ohira M., Sugimura T., Hirohashi S. Retrospective study on amplification of N-myc and c-myc genes in pediatric solid tumors and its association with prognosis and tumor differentiation. Lab Invest. 1988 Sep;59(3):321–327. [PubMed] [Google Scholar]