Determination of apoptosis, proliferation status and O6-methylguanine DNA methyltransferase methylation profiles in different immunophenotypic profiles of diffuse large B-cell lymphoma.
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 immunophenotypic profile (GCB) and non-GCB of diffuse large B-cell lymphoma (DLBCL).


METHODS
The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunophenotypic 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).


CONCLUSIONS
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.
Department of Pathology, Faculty of Medicine, Pamukkale University, Denizli, Turkey Phone: +90 258 361 39 16 E-mail: sennilay@hotmail.com.
Nilay
N
Şen Türk
Nazan
N
Özsan
Vildan
V
Caner
Nedim
N
Karagenç
Füsun
F
Düzcan
Ender
E
Düzcan
Mine
M
Hekimgil