title: Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma.
abstract: The International Neuroblastoma Pathology Classification (INPC) has a prognostic impact that distinguishes two categories of neuroblastoma: favorable histology (FH) and unfavorable histology (UH). We analyzed 92 cases of neuroblastoma with the INPC evaluation and genomic grouping to investigate the correlation between the INPC and genomic signature, together with their prognostic significance. The correlation of UH tumor and partial gains and/or losses (GGP), as well as the correlation of FH tumor and whole gains and/or losses (GGW), was statistically significant. Both UH and GGP were late-onset (median age at diagnosis was 36 and 48 months, respectively) and had poor prognosis (overall survival rate [OS], 43.1% and 42.4%, respectively). In contrast, both FH and GGW were early-onset (median age at diagnosis, 4 and 9.5 months, respectively) and had favorable prognosis (OS, 88.6% and 87.1%, respectively). Unfavorable histology and GGP had significantly inferior OS compared to FH and GGW. Overall survival was not significantly different among the genomic groups in FH; however, it was inferior in UH with GGP. In UH with a single copy MYCN, genomic subgroups GGP2s (both 1p and 11q losses) and GGP3s (partial 11q loss but not 1p loss) indicated significantly poor prognosis compared to GGP4s (no partial 1p and 11q loss). As INPC and MYCN amplification were found to be the most powerful prognostic biological factors, they should be included with genomic grouping as treatment stratification for patients with UH and single copy of MYCN.
authors.affiliation: Department of Pathology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakazawa
authors.affiliation: Department of Pathology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Haga
authors.affiliation: Laboratory of Cancer Genomics, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.affiliation: Department of Pathology, National Center for Child Health and Development, Tokyo, Japan.|Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kamijo
authors.affiliation: Saga-ken Medical Center Koseikan, Saga, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D005784:Gene Amplification; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: Array comparative genomic hybridization; neuroblastoma; pathology; risk assessment; risk factors
references.citation: Maris JM, Hogarty MD, Bagatell R et al. Neuroblastoma. Lancet 2007; 369: 2106-20.
references.citation: Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 2003; 3: 203-16.
references.citation: Cohn SL, Pearson ADJ, London WB et al. The international neuroblastoma risk group (INRG) classification system: an INRG task force report. J Clin Oncol 2009; 27: 289-97.
references.citation: Shimada H, Ambros IM, Dehner LP et al. The International Neuroblastoma Pathology Classification (the Shimada System). Cancer 1999; 86: 364-72.
references.citation: Janoueix-Lerosey I, Schleiermacher G, Michels E et al. Overall genomic pattern is a predictor of outcome in neurpblastoma. J Clin Oncol 2009; 27: 1026-33.
references.citation: Spitz R, Oberthuer A, Zapatka M et al. Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome. Genes Chromosom Cancer 2006; 45: 1130-42.
references.citation: Tomioka N, Oba S, Ohira M et al. Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature. Oncogene 2008; 27: 441-9.
references.citation: Shimada H, Stram DO, Chatten J et al. Identification of subsets of neuroblastoma by combined histopathologic and N-myc analysis. J Natl Cancer Inst 1995; 87: 1470-6.
references.citation: Kaneko M, Tsuchida Y, Mugishima H et al. Intensified chemotherapy increases the survival rates in patients with stage 4 neuroblastoma with MYCN amplification. J Pediatr Hematol Oncol 2002; 24: 613-21.
references.citation: Matsumura T, Michon J. Treatment of localized neuroblastoma. In: Brodeur GM, Sawada T, Tsuchida Y, Voûte PA, eds. Neuroblastoma. Amsterdam: Elsevier, 2000; 403-15.
references.citation: 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: 1471-82.
references.citation: Shimada H, Nakagawa A, Peter J et al. TrkA expression in peripheral neuroblastic tumors. Prognostic significance and biological relevance. Cancer 2004; 101: 1873-81.
references.citation: Caren H, Kryh H, Nethander M et al. High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset. Proc Natl Acad Sci U S A 2010; 107: 4323-8.
references.citation: Sausen M, Leary RJ, Jones S et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat Genet 2013; 45: 12-7.
references.citation: 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: 1466-77.
references.citation: Children's Oncology Group Neuroblastoma Risk Grouping. [Cited 15, December, 2014] Available from URL: http://www.cancer.gov/cancertopics/pdq/treatment/neuroblastoma/healthProfessional/Page4/