Clinical significance of nuclear factor κB and chemokine receptor CXCR4 expression in patients with diffuse large B-cell lymphoma who received rituximab-based therapy

Korean J Intern Med. 2014 Nov;29(6):785-92. doi: 10.3904/kjim.2014.29.6.785. Epub 2014 Oct 31.

Abstract

Background/aims: This study investigated the expression of nuclear factor κB (NF-κB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.

Methods: Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-κB (IκB kinase α, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+).

Results: The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-κB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-κB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-κB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-κB or CXCR4 expression and survival was observed.

Conclusions: The current study suggests that the tissue expression of NF-κB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.

Keywords: CXCR4; Lymphoma; NF-kappa B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Chi-Square Distribution
  • Cyclophosphamide / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / chemistry
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • NF-kappa B / analysis*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prednisone / administration & dosage
  • Proportional Hazards Models
  • Receptors, CXCR4 / analysis*
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Time Factors
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • CXCR4 protein, human
  • NF-kappa B
  • R-CHOP protocol
  • Receptors, CXCR4
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone