Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B‐cell lymphoma

Abstract

Summary. Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of tumours, varying in clinical features, immunophenotype and cytogenetics. The aim of this study was to investigate the prognostic significance of BCL6 gene rearrangement at the 3q27 locus in patients with primary nodal disease, and to examine interrelationships with immunophenotype and International Prognostic Index (IPI). We have developed a fluorescent in situ hybridization (FISH)-based technique for the retrospective analysis of the effect of BCL6 gene rearrangements on survival, using nuclei extracted from paraffin-embedded tissue. FISH results were obtained in 111 presentation cases of nodal DLBCL. The IPI was calculated and each case was stained immunocytochemically for BCL6, BCL2 and CD10. 3q27 rearrangements were detected in 25% of cases. BCL2 protein and a germinal centre (GC) phenotype (defined as CD10 + , BCL6 + ) were expressed in 56% and 41% of cases respectively. In multivariate analysis, rearrangement of 3q27 and BCL2 expression and the absence of a GC phenotype were associated with a poor prognosis. These factors can be used in conjunction with the IPI to improve risk stratification in nodal DLBCL.

Most primary adrenal lymphomas are diffuse large B-cell lymphomas with non-germinal center B-cell phenotype, BCL6 gene rearrangement and poor prognosis

“…18 In Taiwanese patients with diffuse large B-cell lymphomas, Chen et al 15 found no association between BCL6 gene alternations and clinical characteristics (including nodal vs extranodal tumors) or prognosis, probably because the case number with BCL6 gene rearrangement was small (10 of 59 cases). In contrast to these studies, Barrans et al 16 identified rearrangements of the BCL6 locus in 25% diffuse large B-cell lymphomas and found this to be associated with a poor prognosis. In our series of primary adrenal lymphoma, although the case number was small, we have observed a high frequency of BCL6 rearrangement in diffuse large Bcell lymphoma patients (5/6 or 83%) and a poor prognosis.…”

“…[12][13][14][15] It is more frequently detected in diffuse large B-cell lymphomas with an activated Bcell/non-germinal center B-cell phenotype than in those with a germinal center B-cell phenotype. 16,17 The significance of BCL6 gene rearrangement in disease presentation and survival is controversial. Using Southern blot analysis, Offit et al 13 Primary adrenal lymphoma A Mozos et al between BCL6 rearrangement and initial features of the disease or clinical outcome.…”

Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

“…We compared this finding with eighteen previous studies which examined the prognostic value of BCL6 expression for DLBCL patients. Of these studies, only Barrans et al (2002) reported a statistically significant reduction of OS in association with positive BCL6 expression in DLBCL patients. Barrans et al's deviant result might be related to their use of the anti-BCL6 n-3 antibody, in contrast to the majority of the other studies which used the same PG-B6p antibody we employed in the present study (e.g.…”

“…Aside from Barrans et al (2002), seven out of the seventeen remaining studies of BCL-6 expression in DLBCL patients reported a significant association between positive expression of BCL-6 and improved OS (e.g. Harada et al, 1999;Braaten et al, 2003;Berglund et al, 2005;Sjo et al, 2007), whereas nine studies did not report any significant difference in OS between positive and negative BCL-6 expression in DLBCL patients (e.g.…”

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma

“…Multiple studies have looked at the expression of bcl-2 using immunostains and most have found no difference in overall survival. 16,23,[27][28][29][30][31][32][33][34][35] However, some studies have found that bcl-2 expression is associated with a significantly worse overall survival, 3,[36][37][38][39][40][41][42] or event-free survival. [29][30][31]36,37 The discrepancies related to bcl-2 expression and prognosis may be related to the underlying subgroups of DLBCL.…”