Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French-American-British (FAB) international study group

• Published in: Pediatric Blood & Cancer Vol. 51; no. 3; pp. 369 - 374
• Main Authors: Miles, Rodney R., Raphael, Martine, McCarthy, Keith, Wotherspoon, Andrew, Lones, Mark A., Terrier-Lacombe, Marie J., Patte, Catherine, Gerrard, Mary, Auperin, Anne, Sposto, Richard, Davenport, Virginia, Cairo, Mitchell S., Perkins, Sherrie L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2008
• Subjects: Adult; Bcl2; c-Myc; Cell Proliferation; Child; Germinal Center - pathology; germinal center phenotype; Humans; Immunohistochemistry; Lymphoma, Large B-Cell, Diffuse - pathology; Neoplasm Proteins - analysis; pediatric diffuse large B-cell lymphoma; proliferation; Proto-Oncogene Proteins c-bcl-2 - analysis; Proto-Oncogene Proteins c-myc - analysis
• ISSN: 1545-5009; 1545-5017; 1096-911X
• DOI: 10.1002/pbc.21619

Background Diffuse large B‐cell lymphoma (DLBCL) makes up 10–20% of pediatric non‐Hodgkin lymphoma, and these patients have a significantly better prognosis than adults with DLBCL. The difference in prognosis may be related to clinical, phenotypic, and/or biological differences between adult and pediatric DLBCL. In adult DLBCL, the germinal center (GC) phenotype is associated with a better prognosis than the activated B‐cell (ABC) phenotype. However, a high proliferative index and expression of Bcl2 and c‐Myc protein have all been associated with worse outcomes. While multiple studies have addressed the phenotype and expression patterns of adult DLBCL, relatively little is known about these biological variables in pediatric DLBCL. The goal of this study was to investigate the proliferative index, the relative frequencies of the GC and non‐GC subtypes, and the expression of Bcl2 and c‐Myc protein in a cohort of children with DLBCL treated in a uniform manner. Procedure We performed immunohistochemistry (IHC) for MIB1, CD10, Bcl6, MUM1, Bcl2, and c‐Myc on DLBCL tissue from children treated uniformly in the FAB LMB96 trial (SFOP LMB96/CCG5961/UKCCSG/NHL 9600). Results Compared to published adult DLBCL studies, pediatric DLBCL demonstrated moderate to high proliferation rates (83%), increased c‐Myc protein expression (84%), decreased Bcl2 protein expression (28%), and an increased frequency of the GC phenotype (75%). Conclusions These findings suggest that there are significant biologic differences between pediatric and adult forms of DLBCL, which may contribute to the superior prognosis seen in the pediatric population relative to adult disease. Pediatr Blood Cancer 2008;51:369–374. © 2008 Wiley‐Liss, Inc.