Topo IIα gene alterations correlated with survival in patients with diffuse large B-cell lymphoma

Eur J Clin Invest. 2012 Mar;42(3):310-20. doi: 10.1111/j.1365-2362.2011.02585.x. Epub 2011 Aug 31.

Abstract

Background: Topoisomerase IIα (topo IIα) protein expression has prognostic significance in many cancers. However, it is still unclear whether topo IIα protein expression and gene alterations play roles as prognostic factors in diffuse large B-cell lymphoma (DLBCL).

Materials and methods: We selected 102 patients with DLBCL who were homogeneously treated with CHOP chemotherapy and followed up. Using tissue microarray technology, all of the cases, consisting of 25 germinal centre B-cell-like (GCB) and 77 nongerminal centre B-cell-like (non-GCB) types, were studied. Topo IIα protein expression was detected by immunohistochemistry. Gene copy number of topo IIα was analysed by chromogenic in situ hybridization. Cox regression, chi-square test and Kaplan-Meier statistics were performed using SPSS 15·0.

Results: Topo IIα protein overexpression was found in 91 (91/102, 89·2%) cases, while topo IIα gene amplification was absent in all cases. Chromosome 17 deletion was identified in 3 (3/102, 2·9%) cases, diploid in 66 (66/102, 64·7%) cases and aneuploidy in 33 (33/102, 32·4%) cases. By multivariate analysis, no significant differences in progression-free survival (PFS) and overall survival (OS) were observed in patients with topo IIα protein overexpression (P > 0·05), while chromosome 17 aneuploidy predicted worse PFS and OS (P < 0·001).

Conclusions: These results suggested that chromosome 17 aneuploidy, but not topo IIα protein expression, could predict worse survival in patients with DLBCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aneuploidy
  • Antigens, Neoplasm / genetics*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA Topoisomerases, Type II / genetics*
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Female
  • Gene Amplification / genetics
  • Germinal Center / metabolism
  • Germinal Center / pathology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Statistics as Topic
  • Tissue Array Analysis
  • Young Adult

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • DNA Topoisomerases, Type II