Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee. Pediatr Blood Cancer 2013 Mar;60(3):363-70
Date
06/30/2012Pubmed ID
22744966Pubmed Central ID
PMC3397468DOI
10.1002/pbc.24238Scopus ID
2-s2.0-84872472525 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
Author List
Suganuma R, Wang LL, Sano H, Naranjo A, London WB, Seeger RC, Hogarty MD, Gastier-Foster JM, Look AT, Park JR, Maris JM, Cohn SL, Amann G, Beiske K, Cullinane CJ, d'Amore ES, Gambini C, Jarzembowski JA, Joshi VV, Navarro S, Peuchmaur M, Shimada HAuthor
Jason A. Jarzembowski PhD, MD Senior Associate Dean, CEO CSG, Professor in the Pathology and Laboratory Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ChildChild, Preschool
Female
Genetic Association Studies
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Infant
Kaplan-Meier Estimate
Male
N-Myc Proto-Oncogene Protein
Neuroblastoma
Nuclear Proteins
Oncogene Proteins
Prognosis
Research Report
