BCL6 Rearrangement Detected by FISH Analysis Is a Poor Prognostic Factor in the “Non-Germinal Center Phenotype” of Diffuse Large B-Cell Lymphoma.

Takizawa, Jun; Aoki, Sadao; Momoi, Akihito; Kitajima, Toshiki; Higashimura, Masutaka; Nakamura, Naoya; Aizawa, Yoshifusa

doi:10.1182/blood.V108.11.4620.4620

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL), which is the most common type of adult non-Hodgkin lymphoma, is considered to be heterogeneous in cytogenetics, immunophenotype and clinical feature. As the results of gene expression profiling, DLBCL can be divided into prognostically significant 3 subgroups of germinal center B-like (GCB), activated B-like and type 3. Chromosomal translocations affecting the BCL6 locus at the 3q27 locus are common in DLBCL, however, the prognostic significance of BCL6 rearrangement is still controversial.

Methods: Twenty-six cases of DLBCL were examined with interphase fluorescence in situ hybridization (FISH) on touch preparations of lymph nodes using LSI BCL6 dual color probes (Vysis) for the incidence of BCL6 rearrangement and immunohistochemistry on paraffin section using CD10, BCL6 and MUM1 for subclassfying “GCB phenotype” and “non-GCB phenotype”. The correlation of BCL6 rearrangement with survival was investigated in two subgroups of DLBCL.

Results: Of the 26 DLBCL cases, 6 cases (23%) were considered GCB phenotype and 20 cases (77%) non-GCB phenotype. BCL6 rearrangements were detected in 2 of 6 cases (33%) with GCB phenotype and 9 of 20 (45%) with non-GCB phenotype (total 11/26, 42%). ALL 6 cases with the GCB phenotype achieved sustained complete remission after chemotherapy and are alive. On the other hand, complete remission rate was 22% for the cases with BCL6 rearrangement but 73% for the cases without BCL6 rearrangement in the non-GCB phenotype (p=0.069). BCL6 rearrangement had a significant adverse effect on progression free survival within the non-GCB phenotype (P=0.016), but there was no significant correlation between BCL6 rearrangement and overall survival.

Conclusion: FISH-based technique of the BCL6 rearrangements using touch preparations of lymph nodes could be developed for the retrospective analysis on survival. BCL6 rearrangement showed a poor prognostic effect particular in the non-GCB subgroup of DLBCL.