title: Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study.
abstract: OBJECTIVE
  We studied the prognostic significance of bcl2 and p53 protein expression in relation to clinical and pathologic characteristics in patients with diffuse large B-cell lymphoma (LCL).
  
  
  METHODS
  Three hundred seventy-two patients with LCL were retrieved from a population-based registry for non-Hodgkin's lymphoma (NHL). bcl2 and p53 protein expression was studied on paraffin-embedded tumor tissue by immunohistochemistry in relation to clinical factors. Response to therapy and survival were analyzed in 165 patients who were uniformly staged and treated and for whom all prognostic data were available according to the International Prognostic Index (IPI).
  
  
  RESULTS
  Forty-five percent of tumors showed strong expression of the bcl2 protein (bcl2++), with a higher frequency in patients with primary nodal involvement. Disease-free survival (DFS) was significantly better in bcl2-negative/intermediate (bcl2-/+) cases as compared with bcl2++ cases (P = .0011). At 5 years, bcl2-/+ patients showed a DFS rate of 74%, in contrast to bcl2++ patients with a DFS rate of 41% (P = .002). Bcl2 was the strongest independent prognostic value in a multivariate analysis, with a relative risk (RR) of 3.0 in comparison to p53 expression and the clinical factors of the IPI. Overall survival (OS) was not significantly influenced by bcl2 protein expression. p53 protein expression was found in 13% of cases, with a higher frequency in patients with extensive disease. p53 expression did not influence the chance to achieve complete remission (CR) and survival.
  
  
  CONCLUSIONS
  bcl2 protein is frequently expressed in LCL and is a strong independent prognostic factor for DFS. p53 expression is related with high tumor burden, but is not an independent risk factor for CR and survival.
authors.affiliation: Department of Pathology, Leiden University Hospital, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Kramer
authors.forename: J
authors.initials: J
authors.lastname: Hermans
authors.forename: J
authors.initials: J
authors.lastname: Parker
authors.forename: A D
authors.initials: AD
authors.lastname: Krol
authors.forename: J C
authors.initials: JC
authors.lastname: Kluin-Nelemans
authors.forename: H L
authors.initials: HL
authors.lastname: Haak
authors.forename: K
authors.initials: K
authors.lastname: van Groningen
authors.forename: J H
authors.initials: JH
authors.lastname: van Krieken
authors.forename: D
authors.initials: D
authors.lastname: de Jong
authors.forename: P M
authors.initials: PM
authors.lastname: Kluin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53