title: Characterization of childhood precursor T-lymphoblastic lymphoma by immunophenotyping and fluorescent in situ hybridization: a report from the Children's Oncology Group.
abstract: BACKGROUND
  T-lymphoblastic lymphoma (T-LBL) accounts for 25-30% of childhood non-Hodgkin's lymphoma and is closely related to T-lymphoblastic leukemia (T-ALL). Recently, we demonstrated distinct differences in gene expression between childhood T-LBL and T-ALL, but molecular pathogenesis and relevant protein expression patterns in T-LBL remain poorly understood.
  
  
  METHODS
  Children with T-LBL with disseminated disease were registered and treated on COG protocol 5971. Paraffin-embedded tumor tissue was obtained at diagnosis for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) studies. We determined the pattern and intensity of staining for c-Myc, Skp2, Mib-1, p53, TCL-1, bcl-2, and bcl-6 proteins by IHC and c-Myc, p53, bcl-2, bcl-6, and TCR alpha/delta molecular alterations by FISH in 22 pediatric T-LBL cases.
  
  
  RESULTS
  The majority of T-LBL samples expressed Mib-1 (59%) and c-Myc (77%) proteins in greater than 50% of the cells, but Skp2 (14%), p53 (14%), and bcl-2 (23%) expression was less common. FISH studies demonstrated 18% gains and 10% losses in c-Myc, 16% gains in p53, 12% gains and 6% losses in bcl-2, and 6% gains and 19% losses in bcl-6 with little direct correlation between the IHC and FISH studies.
  
  
  CONCLUSIONS
  Childhood T-LBL is a highly proliferative tumor associated with enhanced expression of c-Myc protein, but without detectable c-Myc molecular alterations. FISH studies did not identify consistent etiologies of molecular dysregulation, and future studies with other molecular approaches may be required to elucidate the molecular pathogenesis of childhood T-LBL.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, ARUP Laboratories, Salt Lake City, Utah, USA.
authors.forename: Kristi J
authors.initials: KJ
authors.lastname: Smock
authors.forename: Marilu
authors.initials: M
authors.lastname: Nelson
authors.forename: Sheryl R
authors.initials: SR
authors.lastname: Tripp
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
authors.forename: Minnie
authors.initials: M
authors.lastname: Abromowitch
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
mesh_terms: D002648:Child; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008495:Medical Oncology; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*