Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

Abstract

Background. Diffuse large B-cell lymphoma (DLBCL) amounts for 30-40 % of all adult non-Hodgkin's lymphomas. After R-CHOP immunochemotherapy 40 % of patients develop early relapsed or therapy-refractory disease. The conventional prognostic parameters in DLBCL are not always effective. Therefore, exploring further predictors of disease course remains an issue. Aim. To assess the prognostic value of pAKT1 and рSy< expression in DLBCL. Materials & Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cutoff of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher's exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test). Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index > 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk< expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49-10.9; p < 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54-7.30; p = 0.002). Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk< markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.