Prognostic significance of the Bcl-2 negative germinal centre in patients with diffuse large B cell lymphoma treated with R-CHOP

Abstract

The classification of germinal centre (GC) and non-GC is an important prognostic immunophenotype for patients with diffuse large B cell lymphoma (DLBCL) following anthracycline-based chemotherapy. The expression of the anti-apoptotic protein, Bcl-2, has been associated with an unfavourable prognosis in patients with DLBCL. Immunohistochemistry was performed using antibodies against CD10, Bcl-6, MUM-1 and Bcl-2. To establish the combined prognosis of the immunophenotype and Bcl-2 overexpression, patients were separated into four subgroups based on their gene expression profile: the Bcl-2 positive GC subgroup, Bcl-2 negative GC subgroup, Bcl-2 positive non-GC subgroup, and the Bcl-2 negative non-GC subgroup. The clinical characteristics and survival outcomes of the four patient subgroups were compared. Ninety-six patients with de novo DLBCL received R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin and prednisone) therapy. The baseline characteristics of the patient subgroups were similar. The Bcl-2 negative GC subgroup had a favourable progression-free and overall survival (OS) compared with the other three subgroups (p = 0.042, 0.043). Multivariate analysis confirmed that the Bcl-2 negative GC group was independently associated with progression-free survival and OS. The results of this study showed that the Bcl-2 negative GC patients had the most favourable prognosis among patients with DLBCL that received R-CHOP.

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

“…Likewise IPI score, Karnofsky score and stage showed significant differences between BCL2 protein-positive and -negative group in GCB-DLBCL but not at mRNA level. Consistent with our previous observations and other reports, BCL2-positive cases are observed more frequent in ABC-DLBCL than in GCB-DLBCL (10,22,43). However, the expression of BCL2 mRNA or protein expression was not predictive of either OS or EFS in ABC-DLBCL in our R-CHOP cohort, unlike our CHOP cohort reported previously (12).…”

“…However, other studies have shown a prognostic influence of BCL2 mRNA (42) or protein expression in R-CHOP-treated cohorts (43)(44)(45). Song and colleagues (22) reported significant correlation of BCL2 protein expression with OS in GCB-like DLBCL, whereas Nyman and colleagues showed significance in non-GCB-DLBCL, only marginal (P ¼ 0.07) in GCB-like DLBCL (43). Another report of R-CHOP cohort has indicated that BCL2 protein expression influences relative risk (RR) in OS (RR ¼ 2.…”

“…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.…”

Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP

“…For example, we and others found no significant correlation between the cell of origin and outcome in the patients treated with immunochemotherapy. [17][18][19][20][21][22] In contrast, Fu et al 23 reported a trend towards a better event-free survival and a significantly better overall survival for the patients with the germinal center phenotype as compared with the non-germinal center group of patients. Another approach to immunohistochemically define subgroups of diffuse large B-cell lymphoma has been recently reported by Muris et al 24 Based on the expression of Bcl-2, CD10, and MUM1/IRF4 the algorithm defines the Bcl-2-positive, CD10-negative, and MUM1/IRF4-positive immunophenotype (group 2) as an adverse risk factor for chemotherapy-treated patients.…”

“…11,24,31 However, several studies have not been able to confirm the prognostic impact of the algorithms on survival. [14][15][16][17][18][19][20][21][22] In this study, we focused on the identification of the markers related to the activated B-cell-like phenotype. The importance of the transcription factors MUM1/IRF4 and FOXP-1 as markers for the activated B-cell-like signature is well established.…”