Clinical significance of nuclear factor κB and chemokine receptor CXCR4 expression in patients with diffuse large B-cell lymphoma who received rituximab-based therapy.
OBJECTIVE
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.
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Ho Cheol
HC
Shin
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Jongwon
J
Seo
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Byung Woog
BW
Kang
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Joon Ho
JH
Moon
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Yee Soo
YS
Chae
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Soo Jung
SJ
Lee
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Yoo Jin
YJ
Lee
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Seoae
S
Han
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Sang Kyung
SK
Seo
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Jong Gwang
JG
Kim
Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea.
Sang Kyun
SK
Sohn
Department of Pathology, Kyungpook National University Hospital, Daegu, Korea.
Tae-In
TI
Park
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016328:NF-kappa B / Q000032:analysis*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D019718:Receptors, CXCR4 / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D016328:NF-kappa B; C571759:R-CHOP protocol; D019718:Receptors, CXCR4; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
CXCR4; Lymphoma; NF-kappa B