| Description |
Deregulation of apoptosis plays an important role in normal and malignant lymphopoesis. Survivin is a member of the inhibitor of apoptosis (IAP) family and Akt (protein kinase B) is a serine/threonine kinase involved in the regulation of cell survival signals. But their role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. On the other hand, both molecules and their signaling pathways are targeted by new investigational antineoplastic agents. We studied 46 adult patients with de novo DLBCL.The patients consisted of 29 men and 27 women with a median age of 59 years (range, 24-79). Advanced stage (III/IV) was observed in 24 cases (52%) and the distribution according to the IPI was as follows: low risk, 20 cases (44%); low/intermediate risk, 12 (26%); high/intermediate risk 9 (19%); and high risk, 5 (11%). All patients were treated with curative intent and except one case, an initial treatment started with a chemotherapy regimen CHOP (cyclophosphamide, doxorubicine, vincristine and prednison) with a median of 6 administrated cycles of chemotherapy. Overall response rate was 69% with a complete response (CR) in 31 patients (67%). Patients were also divided into two groups: those with cured disease (31 cases, 54%) and those with fatal course of disease (21 cases, 46%). The median follow-up of the surviving patients was 4,3 years and patients who died from progression of DLBCL was 9 months. Imunohistochemistry was performed on paraffin-embdded tissue sections with a monoclonal antibodies against: Survivin, Akt-1, Akt-2, phospho-Akt-Ser-473 and phospho-Akt-Thr-307. Except survivin, the expression was considered positive if 5% or more of the tumor cells were stained with the antibody, in the case of survivin the cut-off was 20% of positive tumor cells. The Kaplan-Meier method was used to estimate overall (OS) and relaps-free survival (RFS). P-value was based on Gehan-Wilcoxons test or chi-square test and P-values < 0,05 were considered significant. Tumor expression of Survivin and phosphorylated Akt-2 on Ser-473 correlated with an inferior OS and RFS and predicted outcome in patients with DLBCL. Thus, patients with positive expression of Akt-2 phosphorylated on Ser-473 had a median of OS and RFS lower compared to those who were p-Akt-Ser-473 negative (OS: 42 months vs 14 months, p<0,008; RFS: 37 months vs 9 months, p<0,004 ). Similar data were obtained for Survivin (OS: 40 months vs 29 months, p=0,1; RFS: 40 months vs 15 months, p<0,035). All other results were not statistical significant. The results support the proposed key role of Survivin and Akt-2 in regulation of apoptosis with direct impact on clinical outcome of patients with DLBCL.Both molecules are potential targets for therapeutic intervention in DLBCL. Acknowledgment: This project was supported by Internal Grant Agency, Ministry of Health, Czech Republic. No.: NR/8335-3.
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