Imunohistokemijski algoritmi subklasifikacije difuznog B-velikostaničnog limfoma [Immunohistochemical algorithms for diffuse large B cell lymphoma subclassification]

Dotlić, Snježana (2012) Imunohistokemijski algoritmi subklasifikacije difuznog B-velikostaničnog limfoma [Immunohistochemical algorithms for diffuse large B cell lymphoma subclassification]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) is a heterogenous group of aggressive non-Hodgkin lymphomas for which new molecular and immunohistochemical prognostic parameters are needed. This study included 107 patients with DLBCL-NOS stratified into GCB and non-GCB/ABC subgroup according to the immunohistochemical algorithms proposed by Hans et al. and Choi et al. with a purpose to analyse their prognostic value and correlation to other prognostic parameters. Patients in the non-GCB group according to the Hans' algorithm had significantly shorter event free survival, higher frequency of relapse and unfavorable outcome. No prognostic significance was observed after subclassification according to the Choi's algorithm. These results imply that in the observed patient group immunohistochemical subclassification according to the Hans' algorithm offers better prognostic information than Choi's algorithm. This study was also undertaken to test the prognostic significance of CD5 and CD43 markers, as well as c-MYC translocation in DLBCL. Also, the distribution of CD5 and CD43 expression in the GCB and non-GCB/ABC groups was analyzed according to both algorithms. There was no significant correlation between CD5 and CD43 expression and survival, response to therapy or outcome. Prognostic significance of c-MYC translocation could not be analyzed because the incidence of c-MYC translocation in this group of patients was lower than expected. Although the correlation between CD5 and CD43 expression and non-GCB/ABC subgroup did not reach statistical significance, both markers were more frequently distributed in the non-GCB/ABC subgroup. Abberant expression of these markers in tumor cells, as well as correlation between CD43 expression and lack of BCL6 and GCET1 in tumor cells implicates a role these proteins might have in the oncogenesis of the more aggressive form of disease. The study gives a new insight into DLBCL pathogenesis and demonstrates the practical problems in the application of immunohistochemical algorithms in the routine clinical practice.

Abstract in Croatian

Difuzni B-velikostanični limfom, bez osobitosti (DLBCL-NOS) je heterogena skupina agresivnih non-Hodgkinovih limfoma kod kojih postoji potreba za novim prognostičkim parametrima temeljenim na molekularnim osobinama i ekspresiji biljega koji se mogu analizirati imunohistokemijskim metodama. Studija je obuhvatila 107 bolesnika s DLBCL-NOS koji su podijeljeni u GCB i non-GCB/ABC podskupinu prema imunohistokemijskim algoritmima Hans i sur. i Choija i sur. kako bi se ispitala njihova prognostička vrijednost i eventualna povezanost s ostalim prognostičkim parametrima. U podskupini bolesnika s non-GCB imunofenotipom prema algoritmu Hans i sur. nađena je značajna povezanost s lošijim preživljenjem, pojavom relapsa i nepovoljnim ishodom bolesti. Nakon podjele prema Choijevom algoritmu nije utvrđena povezanost GCB i ABC podskupina s preživljenjem, pojavom relapsa niti ishodom. Rezultati pokazuju da u promatranoj skupini bolesnika primjena algoritma prema Hans i sur. pruža korisniju prognostičku informaciju nego algoritam prema Choiju i sur. Analizirano je i prognostičko značenje biljega CD5 i CD43 te translokacije c-MYC kod bolesnika s DLBCL, te njihova korelacija s podjelom na GCB i non-GCB/ABC podskupine prema oba algoritma. Nije utvrđena značajna povezanost s preživljenjem, odgovorom na terapiju ili ishodom bolesti za biljege CD5 i CD43, a analiza prognostičkog značenja translokacije c-MYC nije bila moguća zbog malog broja uzoraka s dokazanom translokacijom. Povezanost ekspresije CD5 i CD43 s non-GCB/ABC podskupinom prema oba algoritma nije bila statistički značajna, iako je uočeno da se oba biljega češće pojavljuju u toj podskupini (75% tumora s dokazanom ekspresijom CD5 bilo je u non-GCB/ABC skupini prema oba algoritma, a 73% i 81% uzoraka s ekspresijom CD43 svrstano je u non-GCB/ABC skupinu prema algoritmu Hans i sur. odnosno Choija i sur.). Aberantna ekspresija ovih biljega u tumorskim stanicama, te češća ekspresija CD43 u BCL6-negativnim i GCET1-negativnim slučajevima DLBCL govori u prilog povezanosti ekspresije CD5 i CD43 s prognostički nepovoljnom skupinom DLBCL i sugerira ulogu ovih proteina u putovima onkogeneze odgovornim za nastanak agresivnijeg oblika bolesti. Ovo istraživanje daje uvid u patogenezu DLBCL-a te dokazuje probleme u primjeni imunohistokemijskih algoritama.

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