Trisomija 3, onkoprotein BCL 10 i MALT želuca kod infekcije s Helicobacter pylori

Gašparov, Slavko (2004) Trisomija 3, onkoprotein BCL 10 i MALT želuca kod infekcije s Helicobacter pylori. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Sixty patients were included in the study, divided in three test groups of 20 patients in each. The main pathomorphological feature of the first group was excessive immunological reaction with the lymphoid nodules or follicles formation (LN/LF) in the gastric mucosa and H. pylori infection present in all subjects of this group. The second group was characterized by the MALT-type lymphoma and 14 of 20 patients had H. pylori. The third group consisted of 20 high grade diffuse large B-cell lymphoma (DLBCL) of the stomach of who 11 had also H. pylori infection. Incidence and severity of H. pylori infection as well as endoscopic findings were evaluated. Aim of the study was to determine the incidence of a specific chromosomal abnormality of trisomy 3 and oncoprotein BCL10 incidence and expression pattern. We were also eventually interested in the correlation of these data with the emergence of therapeutic resistance to the specific "triple" anti-H. pylori treatment. Further aims were to evaluate the importance of these abnormalities on the coursed and outcome of the disease, relation to the formation of the neoplasm and their possible influence on the transformation of MALT–type lymphoma into DLBCL. H. pylori and BCL10 were evaluated by the histological and immunohistological methods respectively that included semiquantitative grading. Trisomy 3 detection was done by FISH on paraffin sections of the endoscopic biopsies. The results have shown that endoscopy is insufficient for the diagnosis of LN/LF and MALT-type lymphoma. We have also found that severity of H. pylori infection does not correlate with the intensity of inflammation, intranuclear expression of BCL10 or presence of trisomy 3 in the cells. Two LN patients exhibited intranuclear expression of BCL10 which we believe, makes them at risk of lymphoma development. Intranuclear expression of BCL10 oncoprotein points to the possible mutation in the BCL10 gene or its rearrangement through chromosomal translocation which all suggests the necessity of introducing cytogenetic and molecular genetic tests in the diagnostic workup. The existence of intranuclear expression of BCL10 in two DLBCL lymphoma patients supports the MALT lymphoma transformation possibility. As no trisomy 3 was found in patients with LN/LF it is most likely that this chromosomal aberration is not responsible for the early phase of autonomous proliferation of lymphoid tissue. More frequent (35% vs. 15%) finding of trisomy 3 in the group II compared to group III argues for the hypothesis that a part of the DLBCL comes from he transformed MALT lymphoma while the rest arises de novo. Trisomy 3 and intranuclear expression of BCL10 were not statistically significant predictors of patients' survival.

Abstract in Croatian

U rad je uključeno 60 bolesnika koji su na temelju histološkog nalaza podijeljeni u tri grupe a u svakoj grupi imamo 20 bolesnika. Glavno morfološko obilježje grupe I je prekomjerna imunološka reakcija tj. LN/LF, a u svih bolesnika prisutan je H. pylori. MALT-tip limfoma je karakteristika grupe II, gdje je od 20 bolesnika H. pylori bio prisutan u 14. U grupi III, od 20 bolesnika s DLBCL želuca H. pylori je nađen u 11. Osim prisutnosti i količine H. pylori zanimali su nas i endoskopski nalazi svih bolesnika. Cilj nam je bio utvrditi u sve tri grupe bolesnika, postojanje citogenetskih (BCL10) i kromosomskih abnormalnosti (trisomija 3), te eventualno, njihov utjecaj na rezistenciju na “triple” terapiju. Također nas je zanimao utjecaj ovih abnormalnosti na tijek i ishod bolesti, povezanost s nastankom tumora, te njihov eventualni utjecaj na transformaciju MALT-tip limfoma u DLBCL. H. pylori smo odredili histološki semikvantitativnom metodom, ekspresiju BCL10 imunohistokemijski a prisutnost trisomije 3 FISH metodom. Na temelju rezultata, pokazalo se da je endoskopski nalaz insuficijentan u dijagnostici LN/LF i MALT-tip limfoma. Zaključili smo da količina H. pylori nije povezana s intenzitetom upale, s intranuklearnom ekspresijom BCL10, kao niti s trisomijom 3. Kako smo intranuklearnu ekspresiju BCL10 našli u 2 bolesnika s LN, mišljenja smo da se radi o bolesnicima rizičnim za nastanak limfoma. Pozitivna intranuklearna ekspresija BCL10 u 60% bolesnika s MALT-tip limfomom govori za mutaciju i/ili translokaciju kromosoma, te bi citogenetsku obradu trebalo uvesti u rutinske dijagnostičke pretrage. U prilog transformacije MALT-tip limfoma u visokomaligni limfom, indirektno govori prisustvo intranuklearne ekspresije BCL10 u 2 bolesnika s DLBCL. Kako trisomiju 3 nismo našli niti u jednog bolesnika s LN/LF, očito je da ova kromosomska promjena nije odgovorna za ranu fazu autonomne proliferacije limfatičnog tkiva. Učestaliji nalaz trisomije 3 u bolesnika grupe II (35%) u odnosu na grupu III (15%) govori u prilog mišljenju da dio DLBCL nastaje transformacijom MALT-tip limfoma, dok drugi dio najvjerojatnije nastaje de novo. Trisomija 3, i intranuklearna ekspresija BCL10 se nisu pokazali kao statistički značajni prediktori preživljenja.

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