Proteinska ekspresija diferencijacijskih gena, translokacija t(14; 18)(q32; q21) i abnormalnosti regije 3q27 u primarnom difuznom B velikostaničnom i folikularnom limfomu stupnja 3

Borovečki, Ana (2007) Proteinska ekspresija diferencijacijskih gena, translokacija t(14; 18)(q32; q21) i abnormalnosti regije 3q27 u primarnom difuznom B velikostaničnom i folikularnom limfomu stupnja 3. PhD thesis, Sveučilište u Zagrebu.

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Abstract

73 patients with lymph nodes enlargement were classified, according WHO lymphoma classification into DLBCL (53 cases) and FL-3 predominantly follicular arhitecture, >75% (20 cases). Expression of markers was detected by immunohistochemical method and cytogenetic abnormalities were analysed by FISH. The results have shown no differences in survival of DLBCL and FL-3 predominantly follicular arhitecture, >75%, which are two different morphological entities according WHO classification, but differences in patients age and IPI were detected. In cases of DLBCL and FL-3 were not found differences in BCL2, BCL6 genes abnormalities and BCL2 protein expression. The BCL6 protein expression was more frequently found in FL-3. Morphological entities DLBCL and FL-3 were equal represent in GCB and ABC groups, which were defined according CD10, BCL6, MUM1/IRF4 and CD138 expression. The t(14;18)(q32;q21) was more frequently found in the GCB group, and t(14;18)(q32;q21) with additional BCL2 signals or only additional BCL2 and IgH signals in the ABC group. t(14;18)(q32;q21) represent an initial mechanism in the pathogenesis of GCB group. Amplification of BCL2 gene is frequently present in ABC group. In the GCB and ABC groups were not detected differences in BCL6 gene abnormanlities. Multivariate regression analysis was shown no prognostic significance of the expression of each BCL6 and CD10 protein expression, the BCL2 and BCL6 genes abnormalities and the IPI. Also in GCB and ABC groups were not detected differences in the IPI. GCB and ABC immunophenotype groups were defined as independent prognostic predictors.

Abstract in Croatian

73 bolesnika s povećanim limfnim čvorovima klasificirani su prema kriterijima SZO klasifikacije u DLBCL (53 bolesnika) i FL-3 pretežno folikularnog rasta, >75% (20 bolesnika). Ekspresija biljega je određena imunohistokemijskom metodom, a citogenetske abnormalnosti FISH metodom na parafinskim rezovima tkiva. Rezultati su pokazali da DLBCL i FL-3 pretežno folikularnog rasta, >75%, iako dva morfološki različita entiteta prema kriterijima SZO klasifikacije, ne pokazuju statistički značajne razlike u preživljenju, ali postoji značajna razlika u dobi bolesnika i vrijednosti MPI. Slučajevi DLBCL i FL-3 nisu se razlikovali u promjenama BCL2, BCL6 gena i ekspresije BCL2 proteina, dok je prisutnost ekspresije proteina BCL6 statistički značajno veća u slučajevima FL-3. Važno je istaknuti da morfološki entiteti DLBCL i FL-3 nisu prepoznatljivi u imunofenotipskim skupinama GCB i ABC, klasificiranim temeljem ekspresije četiri diferencijacijska biljega CD10, BCL6, MUM1/IRF4 i CD138. t(14;18)(q32;q21) nađena je značajno češće u GCB skupini, a t(14;18)(q32;q21) i dodatni BCL2 signali ili samo dodatni BCL2 i IgH signali u ABC skupini. t(14;18)(q32;q21) predstavlja primarni događaj u patogenezi GCB skupine. Mehanizmi amplifikacije BCL2 gena, povezani s progresijom tumora i lošijim kliničkim ishodom, češći su u ABC skupini. Nisu nađene razlike u promjenama BCL6 gena u GCB i ABC skupini. Multivarijatnom regresijskom analizom nije utvrđen prognostički značaj ekspresije pojedinih biljega BCL6 i CD10, analiziranih promjena BCL2 i BCL6 gena, niti MPI. Nije nađena razlika u zastupljenosti skupina rizika MPI između bolesnika s GCB odnosno ABC imunofenotipom. Imunofenotipski karakterizirane skupine GCB i ABC su prognostički značajan pokazatelj.

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