GCB Group Research Articles

Subgrouping and outcome prediction of diffuse large B-cell lymphoma by immunohistochemistry

To categorize diffuse large B-cell lymphoma (DLBCL) into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subgroups by immunohistochemistry; and to investigate the underlying prognostic significance. Immunohistochemical study for CD10, bcl-6 and MUM1 was performed on 133 cases of DLBCL. The cases were then categorized into GCB and non-GCB subgroups. The 5-year overall survival and 5-year progression-free survival rates were compared between the GCB and non-GCB groups, and among the cases with different immunohistochemical expression or with different IPI. Amongst the 133 case studied, CD10 was expressed in 33.1%, while bcl-6 was positive in 34.6% and MUM1 in 45.1%. CD10 expression had a favorable impact on 5-year overall survival (P=0.041) and 5-year progression-free survival (P=0.031). On the other hand, bcl-6 expression had a favor able impact on 5-year progression-free survival (P=0.044). Expression of MUM1 carried an adverse effect on 5-year overall survival (P=0.031) and 5-year progression-free survival (P=0.028). GCB immunophenotype was demonstrated in 40.6% of the cases, while 59.4% showed a non-GCB profile. GCB DLBCL had a significantly longer 5-year overall survival (P=0.004) and 5-year progression-free survival (P=0.003), as compared with the non-GCB group. When dividing the cases into two groups according to their IPI score (IPI=0 to 1 and IPI=2 to 5), it turned out that the 5-year overall and progression-free survival rates of the GCB group were significantly higher than those of the non-GCB group (P=0.019 and 0.014 respectively in cases with IPI of 0 to 1 and P=0.006 and 0.009 respectively in cases with IPI of 2 to 5). The non-GCB cases with a IPI of 2 to 5 had the poorest prognosis. DLBCL subgrouping by immunohistochemistry and analysis of the subgrouping with IPI is feasible and useful in predicting clinical outcome.

A phase II study of R-CHOP in treatment of diffuse large B-cell lymphoma (DLBCL) subgroups

17540 Background: Recent studies with genes expression profiling and tissue microarray have divided the diffuse large B cell lymphoma (DLBCL) into prognostically important subgroups with germinal center B cell like (GCB) and non-GCB. However, these results are based on the samples of patients who were received standard CHOP regimen. Combination with CHOP and Rituximab (R-CHOP) has been proved to improve the survival of patients with DLBCL. To evaluate the efficacy of R-CHOP in different subgroups of DLBCL, this phase II study has been conducted. Methods: Previously untreated patients with DLBCL were enrolled in this study. No upper age limit was specified. Patients received six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 40 mg/m2 for 5 days) every 3 weeks. Immunohistochemical stains on paraffin-embedded tissues from diagnostic biopsies from these patients with antibodies against GCB cell (CD10 and Bcl-6) and activation (MUM1). These patients are divided into GCB and non-GCB groups according to the expression of antibodies against CD10, BCL-6 and MUM1. Results: A total of 64 patients were evaluated, 19 in GCB group and 45 in non-GCB group. Complete Remission (CR) rate was achieved 57.9% and 53.3%, in GCB group and in non-GCB group, respectively. (p = 0.737). A median follow-up of 2.2 years, the two-year failure free survival was no different between two groups (p = 0.566). Conclusions: In patients with GCB group or non-GCB group of DLBCL, addition of Rituximab in CHOP regimen, preliminary result was showed in similar response and survival. No significant financial relationships to disclose.

Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray

AbstractDiffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important subgroups with germinal center B-cell–like (GCB), activated B-cell–like (ABC), and type 3 gene expression profiles using a cDNA microarray. Tissue microarray (TMA) blocks were created from 152 cases of DLBCL, 142 of which had been successfully evaluated by cDNA microarray (75 GCB, 41 ABC, and 26 type 3). Sections were stained with antibodies to CD10, bcl-6, MUM1, FOXP1, cyclin D2, and bcl-2. Expression of bcl-6 (P < .001) or CD10 (P = .019) was associated with better overall survival (OS), whereas expression of MUM1 (P = .009) or cyclin D2 (P < .001) was associated with worse OS. Cases were subclassified using CD10, bcl-6, and MUM1 expression, and 64 cases (42%) were considered GCB and 88 cases (58%) non-GCB. The 5-year OS for the GCB group was 76% compared with only 34% for the non-GCB group (P < .001), which is similar to that reported using the cDNA microarray. Bcl-2 and cyclin D2 were adverse predictors in the non-GCB group. In multivariate analysis, a high International Prognostic Index score (3-5) and the non-GCB phenotype were independent adverse predictors (P < .0001). In summary, immunostains can be used to determine the GCB and non-GCB subtypes of DLBCL and predict survival similar to the cDNA microarray.