Difuzni B-velikostanični limfom (DLBCL) s fenotipom germinalnog centra B stanica (GCB) ima bolju prognozu nego limfom aktiviranih zrelih B-stanica (ABC) fenotip ili tip 3 podskupina. Prethodne studije su navodile da nuklearni faktor-κB (NF- κB) ima značajnu ulogu kod ABC i tip 3 fenotipa, dok GCB fenotip karakteriziraju česte REL amplifi kacije. Upotrebom imunohistokemijske metode analizirali smo kod 99 bolesnika kojima je postavljena dijagnoza DLBCL prisutnost DC10, BCL6 i MUM1, da bismo mogli bolesnike podijeliti u GCB, ABC i tip 3 podskupine, te smo zatim analizirali prisutnu ekspresiju NF- κB u jezgri i u citoplazmi. Kod 22 (22 %) slučajeva prisutna je ekspresija NF-κB u jezgri kod svih podskupina DLBCL. NF-κB ekspresija u citoplazmi prisutna je u svim podskupinama DLBCL i nalazi se kod 77 (77%) bolesnika, i rezultat je značajan. Analizirali smo prisutnost CD10, Bcl6 i MUM1 i prisutnost NF-κB u jezgri i rezultati nisu značajni. Analiza nuklearne akumulacije NF-κB nije povezana ni s jednim kliničkim parametrom uključujući dob, spol, stadij bolesti, primijenjenu terapiju i MPI. Bolesnici s prisutnim NF κB u citoplazmi bez obzira na podskupine prema Hansu i sur. imaju značajno lošije preživljenje nego bolesnici koji nemaju prisutan NF-κB i rezultati su značajni. Bolesnici s GCB fenotipom i negativnom ekspresijom NF-κB u jezgri imaju bolje preživljenje nego bolesnici s GCB fenotipom i pozitivnom ekspresijom NF-κB u jezgri i rezultati su značajni. Bolesnici koji su primali kemoterapiju po shemi R-CHOP i imaju pozitivan NF-κB u jezgri imaju bolje preživljenje, ali rezultati nisu značajni. Ovi rezultati ukazuju na to da NF-κB ekspresija u jezgri i citoplazmi može biti prognostički čimbenik kod DLBCL i to može pojasniti slojevitost rizika kod bolesnika u kombinaciji s GCB / ne-GCB fenotipom. Naša analiza pokazuje da je NF-κB aktivnost kod svih podskupina DLBCL ključna i na taj način može predstavljati obećavajući molekularni cilj za buduće terapije.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 amplifi cations. 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 fi nding was signifi cant. Results: Results on the presence of CD10, BCL6 and MUM1 and the presence of NF-κB in the nucleus were not signifi cant. 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 signifi cantly poorer survival irrespective of the subgroup than patients without cytoplasmic NF-κB, and these results are signifi cant. 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 signifi cant. 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 signifi cant. Discussion and Conclusion: These data suggest that nuclear and cytoplasmic NF-κB expression may be a prognostic factor in DLBCL, thus explaining the stratifi ed 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
