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Neuroblastoma: Biology and staging

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Abstract

Neuroblastoma is the most common extracranial tumor of childhood, with about 650 new cases each year in the United States. The clinical course of neuroblastoma is variable and depends on age at diagnosis, staging, histology, and specific genetic abnormalities, such as MYCN oncogene amplification or aberrations of chromosome 1p or 11q. A subset of tumors will undergo spontaneous regression, whereas others progress despite aggressive therapy. The varied clinical behavior reflects genetic heterogeneity, with many possible gene candidates identified in studies using comparative genetic hybridization arrays, RNA expression microarrays, and genome-wide association studies. Recent studies implicated the anaplastic lymphoma kinase gene in the tumorigenesis of many familial and some sporadic cases of neuroblastoma. The International Neuroblastoma Risk Group developed a new staging and risk classification, with recommendations for analysis of biological markers in neuroblastoma. This review discusses the biology of these tumors, current and new risk classification, and staging recommendations, with a brief outline of preferred treatment strategies.

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References and Recommended Reading

  1. Maris JM, Kyemba SM, Rebbeck TR, et al.: Molecular genetic analysis of familial neuroblastoma. Eur J Cancer 1997, 33:1923–1928.

    Article  CAS  PubMed  Google Scholar 

  2. Bourdeaut F, Trochet D, Janoueix-Lerosey I, et al.: Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Cancer Lett 2005, 228:51–58.

    Article  CAS  PubMed  Google Scholar 

  3. Chen Y, Takita J, Choi YL, et al.: Oncogenic mutations of ALK kinase in neuroblastoma. Nature 2008, 455:971–974.

    Article  CAS  PubMed  Google Scholar 

  4. Janoueix-Lerosey I, Lequin D, Brugieres L, et al.: Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 2008, 455:967–970.

    Article  CAS  PubMed  Google Scholar 

  5. Mosse YP, Laudenslager M, Longo L, et al.: Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 2008, 455:930–935.

    Article  CAS  PubMed  Google Scholar 

  6. Maris JM, Matthay KK: Molecular biology of neuroblastoma. J Clin Oncol 1999, 17:2264–2279.

    CAS  PubMed  Google Scholar 

  7. Attiyeh EF, London WB, Mosse YP, et al.: Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med 2005, 353:2243–2253.

    Article  CAS  PubMed  Google Scholar 

  8. Fujita T, Igarashi J, Okawa ER, et al.: CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst 2008, 100:940–949.

    Article  CAS  PubMed  Google Scholar 

  9. Michels E, Hoebeeck J, De Preter K, et al.: CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC Cancer 2008, 8:173.

    Article  PubMed  Google Scholar 

  10. Spitz R, Hero B, Ernestus K, Berthold F: Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res 2003, 9:52–58.

    CAS  PubMed  Google Scholar 

  11. Vandesompele J, Baudis M, De Preter K, et al.: Unequivocal delineation of clinicogenetic subgroups and development of a new model for improved outcome prediction in neuroblastoma. J Clin Oncol 2005, 23:2280–2299.

    Article  CAS  PubMed  Google Scholar 

  12. Nair PN, McArdle L, Cornell J, et al.: High-resolution analysis of 3p deletion in neuroblastoma and differential methylation of the SEMA3B tumor suppressor gene. Cancer Genet Cytogenet 2007, 174:100–110.

    Article  CAS  PubMed  Google Scholar 

  13. Cohn SL, Pearson AD, London WB, et al.: The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009, 27:289–297.

    Article  PubMed  Google Scholar 

  14. Otto T, Horn S, Brockmann M, et al.: Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell 2009, 15:67–78.

    Article  CAS  PubMed  Google Scholar 

  15. Maris JM: Unholy matrimony: Aurora A and N-Myc as malignant partners in neuroblastoma. Cancer Cell 2009, 15:5–6.

    Article  CAS  PubMed  Google Scholar 

  16. George RE, Sanda T, Hanna M, et al.: Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008, 455:975–978.

    Article  CAS  PubMed  Google Scholar 

  17. Brodeur GM, Pritchard J, Berthold F, et al.: Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993, 11:1466–1477.

    CAS  PubMed  Google Scholar 

  18. Monclair T, Brodeur GM, Ambros PF, et al.: The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol 2009, 27:298–303.

    Article  PubMed  Google Scholar 

  19. Simon T, Hero B, Benz-Bohm G, et al.: Review of image defined risk factors in localized neuroblastoma patients: results of the GPOH NB97 trial. Pediatr Blood Cancer 2008, 50:965–969.

    Article  PubMed  Google Scholar 

  20. Shapiro B, Gross MD: Radiochemistry, biochemistry, and kinetics of 131I-metaiodobenzylguanidine (MIBG) and 123I-MIBG: clinical implications of the use of 123I-MIBG. Med Pediatr Oncol 1987, 15:170–177.

    Article  CAS  PubMed  Google Scholar 

  21. Carlin S, Mairs RJ, McCluskey AG, et al.: Development of a real-time polymerase chain reaction assay for prediction of the uptake of meta-[(131)I]iodobenzylguanidine by neuroblastoma tumors. Clin Cancer Res 2003, 9:3338–3344.

    CAS  PubMed  Google Scholar 

  22. Taggart D, Han MM, Quach A, et al.: Comparison of 123I-Metaiodobenzylguanidine (MIBG) scan and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to evaluate response after 131I-MIBG therapy for neuroblastoma. J Clin Oncol 2009 (in press).

  23. Kushner BH: Neuroblastoma: a disease requiring a multitude of imaging studies. J Nucl Med 2004, 45:1172–1188.

    PubMed  Google Scholar 

  24. Siegel MJ, Ishwaran H, Fletcher BD, et al.: Staging of neuroblastoma at imaging: report of the radiology diagnostic oncology group. Radiology 2002, 223:168–175.

    Article  PubMed  Google Scholar 

  25. Beiske K, Burchill SA, Cheung IY, et al.: Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force. Br J Cancer 2009, 100:1627–1637.

    Article  CAS  PubMed  Google Scholar 

  26. Ambros PF, Ambros IM, Brodeur GM, et al.: International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer 2009, 100:1471–1482.

    Article  CAS  PubMed  Google Scholar 

  27. London WB, Castleberry RP, Matthay KK, et al.: Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children’s Oncology Group. J Clin Oncol 2005, 23:6459–6465.

    Article  CAS  PubMed  Google Scholar 

  28. Schmidt ML, Lal A, Seeger RC, et al.: Favorable prognosis for patients 12 to 18 months of age with stage 4 nonamplified MYCN neuroblastoma: a Children’s Cancer Group Study. J Clin Oncol 2005, 23:6474–6480.

    Article  CAS  PubMed  Google Scholar 

  29. Woods WG, Tuchman M, Robison LL, et al.: A population-based study of the usefulness of screening for neuroblastoma. Lancet 1996, 348:1682–1687.

    Article  CAS  PubMed  Google Scholar 

  30. Schilling FH, Spix C, Berthold F, et al.: Children may not benefit from neuroblastoma screening at 1 year of age. Updated results of the population based controlled trial in Germany. Cancer Lett 2003, 197:19–28.

    Article  CAS  PubMed  Google Scholar 

  31. Hiyama E, Iehara T, Sugimoto T, et al.: Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study. Lancet 2008, 371:1173–1180.

    Article  PubMed  Google Scholar 

  32. Acharya S, Jayabose S, Kogan SJ, et al.: Prenatally diagnosed neuroblastoma. Cancer 1997, 80:304–310.

    Article  CAS  PubMed  Google Scholar 

  33. Franks LM, Bollen A, Seeger RC, et al.: Neuroblastoma in adults and adolescents: an indolent course with poor survival. Cancer 1997, 79:2028–2035.

    Article  CAS  PubMed  Google Scholar 

  34. Kushner BH, Kramer K, LaQuaglia MP, et al.: Neuroblastoma in adolescents and adults: the Memorial Sloan-Kettering experience. Med Pediatr Oncol 2003, 41:508–515.

    Article  PubMed  Google Scholar 

  35. Strenger V, Kerbl R, Dornbusch HJ, et al.: Diagnostic and prognostic impact of urinary catecholamines in neuroblastoma patients. Pediatr Blood Cancer 2007, 48:504–509.

    Article  PubMed  Google Scholar 

  36. Shimada H, Ambros IM, Dehner LP, et al.: Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee. Cancer 1999, 86:349–363.

    Article  CAS  PubMed  Google Scholar 

  37. Sano H, Bonadio J, Gerbing RB, et al.: International neuroblastoma pathology classification adds independent prognostic information beyond the prognostic contribution of age. Eur J Cancer 2006, 42:1113–1119.

    Article  PubMed  Google Scholar 

  38. Berthold F, Boos J, Burdach S, et al.: Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol 2005, 9:649–658.

    Article  Google Scholar 

  39. Matthay KK, Reynolds CP, Seeger RC, et al.: Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol 2009, 27:1007–1013.

    Article  CAS  PubMed  Google Scholar 

  40. Yu AL, London WB, Gilman A, et al.: A phase III randomized trial of chimeric anti-GD2 antibody 14.18 (ch14.18) and cytokine for immunotherapy of high-risk neuroblastoma in first response: Children’s Oncology Group (COG) study ANBL0032. Proc Am Soc Clin Oncol 2009 (in press).

  41. DuBois SG, Matthay KK: Radiolabeled metaiodobenzylguanidine for the treatment of neuroblastoma. Nucl Med Biol. Aug 2008, 35(Suppl 1):S35–S48.

    Article  CAS  PubMed  Google Scholar 

  42. Chesler L, Schlieve C, Goldenberg DD, et al.: Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma. Cancer Res 2006, 66:8139–8146.

    Article  CAS  PubMed  Google Scholar 

  43. Meyer GE, Chesler L, Liu D, et al.: Nordihydroguaiaretic acid inhibits insulin-like growth factor signaling, growth, and survival in human neuroblastoma cells. J Cell Biochem 2007, 102:1529–1541.

    Article  CAS  PubMed  Google Scholar 

  44. Evans AE, Kisselbach KD, Yamashiro DJ, et al.: Antitumor activity of CEP-751 (KT-6587) on human neuroblastoma and medulloblastoma xenografts. Clin Cancer Res 1999, 5:3594–3602.

    CAS  PubMed  Google Scholar 

  45. Keshelava N, Davicioni E, Wan Z, et al.: Histone deacetylase 1 gene expression and sensitization of multi-drug-resistant neuroblastoma cell lines to cytotoxic agents by depsipeptide. J Natl Cancer Inst 2007, 99:1107–1119.

    Article  CAS  PubMed  Google Scholar 

  46. Rubie H, Chisholm J, Defachelles AS, et al.: Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Societe Francaise des Cancers de l’Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study. J Clin Oncol 2006, 24:5259–5264.

    Article  CAS  PubMed  Google Scholar 

  47. Wagner LM, Villablanca JG, Stewart CF, et al.: Phase I trial of oral irinotecan and temozolomide for children with relapsed high-risk neuroblastoma: a new approach to neuroblastoma therapy consortium study. J Clin Oncol 2009, 27:1290–1296.

    Article  CAS  PubMed  Google Scholar 

  48. Villablanca JG, Krailo MD, Ames MM, et al.: Phase I trial of oral fenretinide in children with high-risk solid tumors: a report from the Children’s Oncology Group (CCG 09709). J Clin Oncol 2006, 24:3423–3430.

    Article  CAS  PubMed  Google Scholar 

  49. Nickerson HJ, Matthay KK, Seeger RC, et al.: Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children’s Cancer Group study. J Clin Oncol 2000, 18:477–486.

    CAS  PubMed  Google Scholar 

  50. Schmidt ML, Lukens JN, Seeger RC, et al.: Biologic factors determine prognosis in infants with stage IV neuroblastoma: a prospective Children’s Cancer Group study. J Clin Oncol 2000, 18:1260–1268.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Hematology-Oncology, University of California, San Francisco School of Medicine, M647, 505 Parnassus Avenue, San Francisco, CA, 94143, USA

    Katherine K. Matthay

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  1. Sabine Mueller
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  2. Katherine K. Matthay
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Correspondence to Katherine K. Matthay.

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Mueller, S., Matthay, K.K. Neuroblastoma: Biology and staging. Curr Oncol Rep 11, 431–438 (2009). https://doi.org/10.1007/s11912-009-0059-6

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