Objective: Diffuse large B-cell lymphoma (DLBCL) with germinal center B-cell (GCB) phenotype has better prognosis than activated mature B-cell (ABC) phenotype or type 3 subgroup. Previous studies have reported on a major role of the nuclear factor-κB (NF-κB) in ABC and type 3 phenotypes, whereas GCB phenotype is characterized by frequent REL amplifications.
Methods: In 99 patients diagnosed with DLBCL, the presence of CD10, BCL6 and MUM1 was analyzed by immunohistochemical method to divide them into the GCB, ABC and type 3 subgroups. Then, NF-κB expression was analyzed in the nucleus and cytoplasm. Nuclear NF-κB expression was detected in 22 (22%) cases from all DLBCL subgroups. NF-κB expression in the cytoplasm was recorded in 77 (77%) cases from all DLBCL subgroups and this finding was significant.
Results: Results on the presence of CD10, BCL6 and MUM1 and the presence of NF-xB in the nucleus were not significant. Analysis of nuclear NF-κB accumulation is not associated with any of the clinical parameters including age, sex, stage of disease, therapy administered and IPP. According to Hans et al., patients with NF-κB expressed in the cytoplasm have significantly poorer survival irrespective of the subgroup than patients without cytoplasmic NF-κB, and these results are significant. Patients with GCB phenotype and negative nuclear NF-κB expression have better survival than those with GCB phenotype and positive nuclear NF-κB expression, and these results are also significant. Patients having received chemotherapy according to the R-CHOP schedule and with positive nuclear NF-κB expression have better survival; however, these results are not significant.
Discussion And Conclusion: These data suggest that nuclear and cytoplasmic NF-κB expression may be a prognostic factor in DLBCL, thus explaining the stratified risk observed in patients in combination with GCB/non-GCB phenotype. Our study showed the NF-κB activity to be crucial in all DLBCL subgroups, thus potentially representing a promising molecular target for future therapies.
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Blood Adv
January 2025
Vanderbilt University Medical Center, Nashville, Tennessee, United States.
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