Journals / Turkish Journal of Hematology / 2011 / Cilt: 28 - Sayı: 1

Diffüz büyük B-hücreli lenfomanın farklı immünofenotipik profillerinde apoptozis, proliferasyon durumu ve O6-metilguanin DNA metiltransferaz metilasyon profillerinin tespiti

Determination of apoptosis, proliferation status and O6-methylguanine DNA methyltransferase methylation profiles in different immunophenotypic profiles of diffuse large B-cell lymphoma

Pages
15–26
DOI
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Conclusion: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB.

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Objective & Hypothesis:Objective: Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid), apoptotic index (AI) and proliferation index (PI) in germinal center B-cell-like immu- nophenotypic profile (GCB) and non-GCB of diffuse large B-cell lymphoma (DLBCL).
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Key Findings & Data:Materials and Methods: The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunopheno- typic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases) or non-GCB (72 cases).
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Conclusion & Impact:Conclusion: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB.
🔬Design:Research Article
📍Scope:95 samples
⚙️Variables:Domain Parameters

Abstract

Objective: Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid), apoptotic index (AI) and proliferation index (PI) in germinal center B-cell-like immu- nophenotypic profile (GCB) and non-GCB of diffuse large B-cell lymphoma (DLBCL). Materials and Methods: The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunopheno- typic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases) or non-GCB (72 cases). Apoptosis-associated proteins and PI were determined by IHC, and TUNEL method was used to determine AI. MGMT methylation analysis was performed by real-time PCR. Results: The PI was significantly higher in GCB compared with non-GCB (p=0.011). Percentage of cells stained with bcl-6 was positively correlated with the percentage of cells expressing bcl-2 (p=0.023), AI (p=0.006) and PI (p<0.001), while a significant negative correlation was observed with the percentage of cells expressing bax (p=0.027). The percentage of cells stained with MUM1 showed a significantly positive correlation with the percentage of cells expressing bcl-xl (p=0.003), bid (p=0.002), AI (p<0.001), and PI (p=0.001). MGMT methylation analysis was performed in 95 samples, and methylated profile was found in 31 cases (32.6%). GCB was found in 6 cases (22.2%) and non-GCB was determined in 25 cases (36.8%) out of 31 with MGMT methylated samples. There was no significant association between MGMT methylation status and immunophenotypic profiles (p=0.173). Conclusion: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB. Additionally, we found that apoptosis-associated proteins were not significantly associated with immunophenotypic profiles.

Özet

Amaç: Diffüz büyük B-hücreli lenfoma (DBBHL)’nın germinal merkez B-hücresi benzeri (GCB) ve non-GCB profillerinde apoptozis-ilişkili proteinlerin (bcl-2, bcl-xl, bax, bak, bid) ekspresyonunu, apop- totic indeksi (AI) ve proliferasyon indeksi (PI)’ni araştırmaktır. Ayrıca, O6-methylguanine-DNA meth- yltransferase (MGMT) geninin promoter bölgesinin metilasyon durumunu ve onun DBBHL’nın immünofenotipik diferansiyasyonuyla ilişkisini araştırmaktır. Yöntem ve Gereçler: 101 olgu GCB (29 olgu) ve non-GCB (72 olgu) olarak sınıflandırıldı. Apoptozis- ilişkili proteinler ve PI immünohistokimyasal olarak saptandı ve TUNEL yöntemi AI’i belirlemek için kullanıldı. MGMT metilasyon analizi, real-time PCR ile gerçekleştirildi. Bulgular: PI, non-GCB ile karşılaştırıldığında GCB’de anlamlı şekilde yüksek saptandı (p=0.011). Bcl-6 ile p: PI, non-GCB ile karşılaştırıldığında GCB’de anlamlı şekilde yüksek saptandı (p=0.011). Bcl-6 ile pozitif boyanan hücrelerin yüzdesi bcl-2 (p=0.023), AI (p=0.006), ve PI (p<0.001) eksprese eden hücrelerin yüzdesi ile pozitif şekilde korele iken, bax eksprese eden hücrelerin yüzdesi ile nega- tif korelasyon gözlendi (p=0.027). MUM1 ile boyanan hücrelerin yüzdesi bcl-xl (p=0.003), bid (p=0.002), AI (p<0.001) ve PI (p=0.001) eksprese eden hücrelerin yüzdesi ile anlamlı şekilde pozitif korelasyon gösterdi. MGMT metilasyon analizi 95 örneğe uygulandı ve metilasyon profili 31 olguda (32.6%) saptandı. 31 MGMT metile örnekten 6 olgunun (22.2%) GCB ve 25 olgunun (36.8%) non- GCB olduğu belirlendi. MGMT metilasyon durumu ve immünofenotipik profiler arasında anlamlı ilişki saptanmadı (p=0.173). Sonuç: Bu bulgular, bcl-6 protein ekspresyonunun GCB’de yüksek PI’inden sorumlu olabileceğini öne sürmektedir. Ek olarak, apoptozis-ilişkili proteinlerin immünofenotipik profilerle anlamlı ilişki göstermediğini saptadık.

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Cite This Article

TÜRK, N. Ş., ÖZSAN, N., CANER, V., KARAGENÇ, N., DÜZCAN, F., DÜZCAN, E., HEKİMGİL, M. (2011). Diffüz büyük B-hücreli lenfomanın farklı immünofenotipik profillerinde apoptozis, proliferasyon durumu ve O6-metilguanin DNA metiltransferaz metilasyon profillerinin tespiti. Turkish Journal of Hematology, Cilt: 28 - Sayı: 1, 15–26. https://ajindex.com/articles/412897

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