Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee.

Abstract

BACKGROUND:

Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children's Cancer Group and Children's Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotype-phenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis).

PROCEDURE:

To distinguish prognostic subgroups in the genotype-phenotype discordant pNTs, two subgroups, "conventional" and "bull's eye," were identified based on the nuclear morphology. The "conventional" tumors (35 cases) included: Neuroblastoma, poorly differentiated subtype (NB-PD, 26 cases) with "salt-and-pepper" nuclei; neuroblastoma, differentiating subtype (4 cases); ganglioneuroblastoma, intermixed (3 cases); and ganglioneuroma, maturing subtype (2 cases). The "bull's eye" tumors included NB-PD with prominent nucleoli (16 cases). Clinicopathologic characteristics of these two subgroups were analyzed. N-myc protein expression was tested immunohistochemically on available tumors.

RESULTS:

No significant difference was found between these two subgroups in the distribution of prognostic factors such as age at diagnosis, clinical stage, histopathology category/subtype, mitosis-karyorrhexis index, ploidy, 1p LOH, and unbalanced 11q LOH. However, prognosis of the patients with "conventional" tumors (5-year EFS 85.7 ± 12.2%; OS 89.3 ± 10.3%) was significantly better than those with "bull's eye" tumors (EFS 31.3 ± 13.0%; OS 42.9 ± 16.2%; P = 0.0010 and 0.0008, respectively). Immunohistochemically all (11/11) tested "conventional" tumors were negative, and 10/11 tested "bull's eye" tumors were positive for N-myc protein expression.

CONCLUSIONS:

Based on the presence or absence of prominent nucleoli (the putative site of RNA synthesis/accumulation leading to N-myc protein expression), two prognostic subgroups, "conventional" with a better prognosis and "bull's eye" with a poor prognosis, were distinguished among the genotype-phenotype discordant pNTs.

• Authors: Rie Suganuma, Larry L Wang, Hideki Sano, Arlene Naranjo, Wendy B London, Robert C Seeger, Michael D Hogarty, Julie M Gastier-Foster, A Thomas Look, Julie R Park, John M Maris, Susan L Cohn, Gabriele Amann, Klaus Beiske, Catherine J Cullinane, Emanuele S G d'Amore, Claudio Gambini, Jason A Jarzembowski, Vijay V Joshi, Samuel Navarro, Michel Peuchmaur, Hiroyuki Shimada
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 60 Issue 3 Pg. 363-70 (Mar 2013) ISSN: 1545-5017 [Electronic] United States
• PMID: 22744966 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• MYCN protein, human
• N-Myc Proto-Oncogene Protein
• Nuclear Proteins
• Oncogene Proteins

Topics

• Child
• Child, Preschool
• Female
• Genetic Association Studies
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Infant
• Kaplan-Meier Estimate
• Male
• N-Myc Proto-Oncogene Protein
• Neuroblastoma (classification, genetics, pathology)
• Nuclear Proteins (analysis, genetics)
• Oncogene Proteins (analysis, genetics)
• Prognosis
• Research Report