Polycomb protein EZH2 expression in diffuse large B-cell lymphoma is associated with better prognosis in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone

Leuk Lymphoma. 2014 Sep;55(9):2056-63. doi: 10.3109/10428194.2013.858816. Epub 2014 Feb 24.

Abstract

Polycomb group (PcG) proteins are evolutionarily conserved regulators of gene expression that contribute to normal lymphocyte development, and are involved in malignant transformation of these cells. Recently, BMI1 and EZH2 have been shown to be involved in lymphomagenesis and oncogenesis. We tried to elucidate the role of EZH2 as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). High-level expression of EZH2 (EZH2 ≥ 70%) was associated with superior overall survival (OS) of 85.8% compared to low expression (EZH2 < 70%), with OS of 44.5% (p = 0.005). Subgroup analysis showed that the activated B-cell (ABC) subtype with high EZH2 expression had the highest overall survival (p = 0.011). In analysis of EZH2 expression within low International Prognostic Index (IPI) score, high EZH2 expression had a significant statistical correlation with longer OS (p = 0.034). With high IPI score, high EZH2 expression tended to be associated with longer OS (p = 0.130). Our results showed that EZH2 expression had a high prognostic relevance to survival outcomes. We demonstrated that DLBCL was associated with increased expression of the EZH2 PcG protein and Ki67. The distribution of EZH2 expression was wider than that of Ki67. In summary, increased EZH2 expression of tumor cells was associated with improvements in OS.

Keywords: EZH2; Polycomb protein; diffuse large B-cell lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Mitosis
  • Neoplasm Staging
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Prednisone / therapeutic use
  • Prognosis
  • Retrospective Studies
  • Rituximab
  • Treatment Outcome
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Ki-67 Antigen
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • Prednisone