Prognostic impact of immunohistochemical biomarkers in diffuse large B‐cell lymphoma in the rituximab era

Abstract

We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group ( P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated.

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

“…These results suggest that the SH3BP5 and LMO3 protein expressions may be related to the molecular pathogenesis of DLBCL and that rituximab addition can overcome the negative effect of the expression of these two proteins. Similar data regarding the loss of prognostic value for DLBCL patients treated with R‐CHOP have been reported 12, 13, 14. Rituximab mediates drug‐induced apoptosis via down‐regulation of several signaling pathways and chemosensitization of non‐Hodgkin's lymphoma B‐cells 15.…”

BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab

“…Several recent studies of R-CHOP cohorts have failed to show a BCL2 prognostic effect due to a disproportionate benefit from rituximab of BCL2-positive cases and with no association of BCL2 expression with OS in DLBCL (23)(24)(25). Similarly, a patient cohort treated with rituximab and EPOCH also showed no association of BCL2 with OS or EFS (41).…”

“…Because the standard treatment of DLBCL now includes rituximab, several studies with conflicting observations concerning prognostic value of BCL2 expression in R-CHOP-treated patients have been reported in recent years with some showing (22,23) and some not (24,25) showing any prognostic significance. Therefore, we analyzed our cohort of GEP-defined DLBCL to determine whether BCL2 overexpression still has prognostic value in patients with DLBCL treated in the R-CHOP era.…”

Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL

“…[20][21][22][23][24][25] Likewise, results were contradictory in DLBCL cohorts treated with R-CHOP. 17,[26][27][28] Several reasons may account for these discrepancies. First, retrospective analyses of relatively small series of DLBCL patients with heterogeneous treatment modalities may have confounded the results.…”