[PROGNOSTIC ROLE OF NF-κB EXPRESSION IN DIFFUSE LARGE B-CELL LYMPHOMA SUBGROUPS]

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.

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 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.

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.