PURPOSE: In search for subgroups of diffuse large B-cell lymphoma (DLBCL) with different histogenetic origin and prognosis, as has been described by gene expression profiling, we examined tumor specimens from 125 patients with DLBCL, uniformly treated by either cyclophosphamideAdriamycin-vincristine-prednisone or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin in a multicenter trial set by the Nordic Lymphoma Group 1989-1994. EXPERIMENTAL DESIGN: Bcl-6, CD10, and CD40 were chosen as markers for a germinal center phenotype, CD23 as a marker of pre/early germinal center origin, and CD138 as a marker for postgerminal center origin. In addition, expression of the apoptotic regulators bcl-2 and bax was analyzed. Immunohistochemical analysis was performed using the EnVision method. RESULTS: CD10 was positive in 51%, bcl-6 in 97%, and CD138 only in 2% of the cases. No prognostic conclusions could be drawn from analysis of these factors. CD40 was positive in 76% of the cases. This group was associated with superior time to treatment failure (P = 0.027) and overall survival (OS; P = 0.0068). By Cox regression analysis, positivity for CD40 was shown to be a prognostic factor for OS, independent of International Prognostic Index. CD23 was positive in 16% of the cases (all CD5 negative and all CD40 positive). This group showed a strong tendency for better OS (P = 0.033). CD40 expression correlated with bax but not with bcl-2 expression. CONCLUSIONS: CD23 and CD40 expression seems to be prognostically favorable in DLBCL. This may be secondary to a germinal center origin or attributable to increased apoptosis via induction of bax and/or enhanced T-cell interaction, resulting in improved autologous tumor response. Confirmatory studies are necessary.
PURPOSE: In search for subgroups of diffuse large B-cell lymphoma (DLBCL) with different histogenetic origin and prognosis, as has been described by gene expression profiling, we examined tumor specimens from 125 patients with DLBCL, uniformly treated by either cyclophosphamideAdriamycin-vincristine-prednisone or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin in a multicenter trial set by the Nordic Lymphoma Group 1989-1994. EXPERIMENTAL DESIGN:Bcl-6, CD10, and CD40 were chosen as markers for a germinal center phenotype, CD23 as a marker of pre/early germinal center origin, and CD138 as a marker for postgerminal center origin. In addition, expression of the apoptotic regulators bcl-2 and bax was analyzed. Immunohistochemical analysis was performed using the EnVision method. RESULTS:CD10 was positive in 51%, bcl-6 in 97%, and CD138 only in 2% of the cases. No prognostic conclusions could be drawn from analysis of these factors. CD40 was positive in 76% of the cases. This group was associated with superior time to treatment failure (P = 0.027) and overall survival (OS; P = 0.0068). By Cox regression analysis, positivity for CD40 was shown to be a prognostic factor for OS, independent of International Prognostic Index. CD23 was positive in 16% of the cases (all CD5 negative and all CD40 positive). This group showed a strong tendency for better OS (P = 0.033). CD40 expression correlated with bax but not with bcl-2 expression. CONCLUSIONS:CD23 and CD40 expression seems to be prognostically favorable in DLBCL. This may be secondary to a germinal center origin or attributable to increased apoptosis via induction of bax and/or enhanced T-cell interaction, resulting in improved autologous tumor response. Confirmatory studies are necessary.