Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma

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.

[1]  Bill Bynum,et al.  Lancet , 2015, The Lancet.

[2]  Giovanni Parmigiani,et al.  Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma , 2012, Nature Genetics.

[3]  Staffan Nilsson,et al.  High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset , 2010, Proceedings of the National Academy of Sciences.

[4]  J Khan,et al.  International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee , 2009, British Journal of Cancer.

[5]  Gudrun Schleiermacher,et al.  Overall genomic pattern is a predictor of outcome in neuroblastoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  Barbara Hero,et al.  The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  D Pinkel,et al.  Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature , 2008, Oncogene.

[8]  F. Berthold,et al.  Oligonucleotide array‐based comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome , 2006, Genes, chromosomes & cancer.

[9]  Hong Wang,et al.  TrkA expression in peripheral neuroblastic tumors , 2004, Cancer.

[10]  G. Brodeur Neuroblastoma: biological insights into a clinical enigma , 2003, Nature Reviews Cancer.

[11]  K. Kawa,et al.  Intensified Chemotherapy Increases the Survival Rates in Patients With Stage 4 Neuroblastoma With MYCN Amplification , 2002, Journal of pediatric hematology/oncology.

[12]  K K Matthay,et al.  The International Neuroblastoma Pathology Classification (the Shimada system) , 1999, Cancer.

[13]  D. Stram,et al.  Identification of subsets of neuroblastomas by combined histopathologic and N-myc analysis. , 1995, Journal of the National Cancer Institute.

[14]  F. Berthold,et al.  Revisions of the international criteria for neuroblastoma diagnosis, staging and response to treatment. , 1993, Progress in clinical and biological research.

[15]  J. Ninane,et al.  Treatment of Localized Neuroblastoma , 1986, The American journal of pediatric hematology/oncology.