Search

Chemotherapy and rituximab (R) is current standard therapy in diffuse large B-cell lymphoma (DLBCL), but a substantial proportion of patients still fail to reach sustained remission. In vitro studies have indicated that rituximab resistance could be accompanied by dysregulated apoptotic pathways, such as the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, which can be constitutively activated in DLBCL. In this retrospective, immunohistochemical study on 106 patients treated with R-CHO(E)P (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab [+etoposide]), we investigated the prognostic role of proteins involved in different apoptotic pathways; phosphorylated AKT (p-AKT), bcl-2, MCL1, bcl-xL, Bax and Bak. High p-AKT expression (>108 cells/mm2, highest quartile, n = 27) predicted worse progression-free (PFS) ( P = 0·02) and overall (OS) ( P = 0·01) survival, independent of International Prognostic Index and sex. Also bcl-2+ (cut-off 50%) predicted worse PFS ( P = 0·005) and OS ( P = 0·05) but after adjustment for clinical factors only the influence on PFS ( P = 0·03) remained significant. The prognostic impact of p-AKT overexpression was independent of bcl-2 status. MCL1, bcl-xL, Bax and Bak expression did not add any prognostic information. Our results suggest that high p-AKT expression predicts worse outcome , possibly indicating that inhibition of the activated PI3K/AKT pathway could be of clinical interest in DLBCL patients. In addition, bcl-2 status could have prognostic importance also in the era of immunochemotherapy. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAM) have been ascribed both pro- and anti-tumor properties, but the majority of clinical cancer studies have shown that the presence of a high number of TAM is related to poor prognosis, suggesting that TAM predominantly exert pro-tumoral activity. The prognostic role of TAM in patients with diffuse large B-cell lymphoma (DLBCL), however, is so far unknown. Therefore, TAM were immunohistochemically stained with a CD68 antibody in a retrospective, population-based study including 176 DLBCL patients treated with curative intent. With the exception that patients >60 years of age had a larger number of CD68+ cells (1143 vs 1018 cells/mm2; P = 0.05), no significant differences were found between the number of CD68+ cells and other clinical factors. Similarly, germinal center B-cell (GCB)/non-GCB immunophenotype or low/high Ki-67 percentage were not associated with CD68 expression. Finally, no significant correlation was found between the number of CD68+ cells and progression-free survival ( P = 0.34) or overall survival ( P = 0.94). These data indicate that the pro-tumor effect of TAM has limited clinical relevance in DLBCL patients, which could imply that therapeutic strategies aimed at enhancing their anti-tumor activity are of continuous clinical interest. [ABSTRACT FROM AUTHOR]

The prognostic role of overexpression of Ki-67 protein in diffuse large B-cell lymphoma (DLBCL) is still unclear. Furthermore, immunohistochemical studies have suggested a correlation between markers of proliferation, B-cell differentiation and apoptosis, but the prognostic relevance of these findings has not been clarified. To investigate the prognostic impact of Ki-67, in the context of this correlation, a retrospective immunohistochemical study was performed on 199 DLBCL patients treated with curative intent. Patients with low Ki-67 expression (<49%) had significantly worse progression-free (PFS) and overall (OS) survival, independent of clinical risk factors. In addition, low Ki-67 correlated to bcl-2 expression but not to non-germinal centre B-cell-like (non-GCB) phenotype. Each of these factors had negative impact on PFS and OS, but low Ki-67 expression also remained as an adverse prognostic factor independent of non-GCB phenotype and bcl-2 expression. Together, these results suggest that low rather than high Ki-67 protein expression is of prognostic importance in DLBCL. [ABSTRACT FROM AUTHOR]