title: Expression of p53, c-Myc, or Bcl-6 suggests a poor prognosis in primary central nervous system diffuse large B-cell lymphoma among immunocompetent individuals.
abstract: BACKGROUND
  Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) in immunocompetent individuals, although rare, has been rising in incidence. Currently, no reliable prognostic markers are available for these individuals.
  
  
  OBJECTIVE
  To study the implications of expression of a panel of oncogenic proteins (Bcl-2, Bcl-6, and c-Myc) and p53 for predicting clinical outcome, particularly overall survival, in immunocompetent individuals with primary CNS DLBCL.
  
  
  METHODS
  Fourteen primary CNS DLBCL cases were retrospectively studied by immunohistochemistry on formalin-fixed, paraffin-embedded sections for the expression of c-Myc, Bcl-2, Bcl-6, and p53.
  
  
  RESULTS
  The overall frequencies of expression for p53, c-Myc, Bcl-2, and Bcl-6 in these cases were 29%, 50%, 71%, and 57%, respectively. Cases with expression of p53, c-Myc, or Bcl-6 had a poorer overall survival than those without (Kaplan-Meier survival analysis: 50% cumulative overall survival, 2 months vs 30-60 months, P =.02, log-rank test; 9-16 months vs 21-60 months, P =.03, log-rank test; and 9-16 months vs 21-60 months, P =.16, log-rank test, respectively). The expression of Bcl-2 or proliferation activity by MIB-1 showed no correlation with overall survival. Likewise, the clinical parameters, including age, location of tumors, multiplicity of tumor lesions, and lactase dehydrogenase levels revealed no impact on overall survival.
  
  
  CONCLUSIONS
  Our results suggest that patients with expression of p53, c-Myc, or Bcl-6 have a poorer overall survival than those without. Since traditional prognostic markers in non-CNS DLBCL, such as staging and International Prognostic Index scores, are not applicable to primary CNS DLBCL, evaluation of p53, c-Myc, and Bcl-6 by immunohistochemistry may be warranted as part of prognostic evaluation in immunocompetent patients with primary CNS DLBCL. Further studies are indicated to confirm our observations.
authors.affiliation: Department of Pathology, Medical College of Wisconsin, Milwaukee 53226, USA. jeffchang@pol.net
authors.forename: Chung-Che
authors.initials: CC
authors.lastname: Chang
authors.forename: Bal
authors.initials: B
authors.lastname: Kampalath
authors.forename: Christopher
authors.initials: C
authors.lastname: Schultz
authors.forename: Ellen
authors.initials: E
authors.lastname: Bunyi-Teopengco
authors.forename: Brent
authors.initials: B
authors.lastname: Logan
authors.forename: Camellia
authors.initials: C
authors.lastname: Eshoa
authors.forename: Ayse P
authors.initials: AP
authors.lastname: Dincer
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000276:immunology; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007121:Immunocompetence / Q000502:physiology; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000276:immunology; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000276:immunology; D012189:Retrospective Studies; D016019:Survival Analysis; D016707:Tissue Fixation; D014157:Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D005557:Formaldehyde