Korean J Intern Med.  2014 Nov;29(6):785-792. 10.3904/kjim.2014.29.6.785.

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

• Shin HC
• Seo J
• Kang BW
• Moon JH
• Chae YS
• Lee SJ
• Lee YJ
• Han S
• Seo SK
• Kim JG
• Sohn SK
• Park TI

• KMID: 2070136
• DOI: http://doi.org/10.3904/kjim.2014.29.6.785

Abstract

BACKGROUND/AIMS
This study investigated the expression of nuclear factor kappaB (NF-kappaB) 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-kappaB (IkappaB kinase alpha, 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-kappaB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-kappaB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-kappaB 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-kappaB or CXCR4 expression and survival was observed.
CONCLUSIONS
The current study suggests that the tissue expression of NF-kappaB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.

Keyword

Lymphoma; NF-kappa B; CXCR4

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Murine-Derived/administration & dosage
Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
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/*drug therapy/mortality/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
Time Factors
Treatment Outcome
Tumor Markers, Biological/*analysis
Vincristine/administration & dosage
Young Adult
Antibodies, Monoclonal, Murine-Derived
Cyclophosphamide
Doxorubicin
NF-kappa B
Prednisone
Receptors, CXCR4
Tumor Markers, Biological
Vincristine