title: Comparison of ataxia-telangiectasia mutated protein expression in diffuse large B-cell lymphomas of primary central nervous system and non-central nervous system origin.
abstract: BACKGROUND
  The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd phosphoprotein known to be associated with chromosomal regions containing double-strand breaks. The mutations in the ATM gene may be involved in the development of some subtypes of sporadic lymphomas and leukemias. In primary central nervous system diffuse large B-cell lymphomas (PCNS DLBCLs), the pathogenetic role of ATM mutation has not been investigated.
  
  
  OBJECTIVE
  To investigate ATM protein expression in PCNS DLBCLs, in comparison with that in non-central nervous system (non-CNS) DLBCLs and to study the relationship of ATM protein loss with several clinicopathologic parameters.
  
  
  METHODS
  This study included 42 cases of PCNS DLBCL and 33 cases of non-CNS DLBCL from immunocompetent patients. The ATM protein loss was analyzed by immunohistochemical staining. For the subclassification of DLBCL and analysis of the relationship between ATM and other prognostic markers, we performed immunohistochemical evaluation to detect the following markers: Bcl-6, CD10, multiple myeloma-1, CD138, Bcl-2, Ki-67, and p53.
  
  
  RESULTS
  The loss of ATM expression was statistically more frequent in PCNS DLBCLs (21/42 cases [50.0%]) than in non-CNS DLBCLs (0/33 cases [0.0%]; P < .001). The loss of ATM expression was not a prognostic marker in PCNS DLBCLs (P = .64). The loss of ATM expression had a strong correlation with the germinal center B-cell-like subtype (P = .01), a low Ki-67 labeling index (P = .03), and low Bcl-2 expression (P = .01) among several clinicopathologic parameters.
  
  
  CONCLUSIONS
  Our results suggest that the ATM protein is more strongly correlated with PCNS DLBCL lymphomagenesis than with non-CNS DLBCLs, especially in germinal center B-cell-like subtypes demonstrating low Ki-67 labeling indexes and low Bcl-2 expression.
authors.affiliation: Department of Pathology, College of Medicine, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea 120-752.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: June-Won
authors.initials: JW
authors.lastname: Cheong
authors.forename: Kwang Hwa
authors.initials: KH
authors.lastname: Park
authors.forename: Tai Seung
authors.initials: TS
authors.lastname: Kim
authors.forename: Woo-Ick
authors.initials: WI
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D025521:Tumor Suppressor Proteins; C067169:RPL22 protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases