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Comparative Study
. 2010 Jan;95(1):96-101.
doi: 10.3324/haematol.2009.007203. Epub 2009 Oct 1.

Correlations between BCL6 rearrangement and outcome in patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP

Jesse Shustik  1 , Guangming Han, Pedro Farinha, Nathalie A Johnson, Susana Ben Neriah, Joseph M Connors, Laurie H Sehn, Douglas E Horsman, Randy D Gascoyne, Christian Steidl
Affiliations
Comparative Study

Correlations between BCL6 rearrangement and outcome in patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP

Jesse Shustik et al. Haematologica. 2010 Jan.

Abstract

Background: BCL6 gene rearrangement is the most frequent chromosomal abnormality in diffuse large B-cell lymphoma, a malignancy characterized by genetic heterogeneity and wide variability in clinical outcome. The prognostic significance of BCL6 rearrangement has not been evaluated in the context of rituximab therapy for diffuse large B-cell lymphoma. We analyzed the effect of the BCL6 rearrangement on survival in patients with diffuse large B-cell lymphoma treated with CHOP and CHOP plus rituximab (R-CHOP).

Design and methods: BCL6 rearrangement status was analyzed by fluorescence in situ hybridization with break-apart probes in 164 patients with diffuse large B-cell lymphoma treated with CHOP (n=65) or R-CHOP (n=99). Cell-of-origin immunophenotype including BCL6 protein expression were determined by immunohistochemistry on a tissue microarray.

Results: BCL6 rearrangement was detected in 19.5% of cases. The presence of the gene rearrangement was associated with a non-germinal center B-cell immunophenotype (P=0.006), and showed no correlation with BCL6 protein expression. A trend toward inferior overall survival was observed in association with the BCL6 rearrangement among patients treated with R-CHOP (P=0.08), but not among patients treated with CHOP (P=0.64). However, BCL6 rearrangement also correlated with a high International Prognostic Index score (P=0.02), and did not demonstrate independent prognostic value by multivariate analysis.

Conclusions: The introduction of rituximab may have altered the prognostic impact of BCL6 gene rearrangement in patients with diffuse large B-cell lymphoma. However, prospective analysis within large randomized clinical trials will be needed to clarify the prognostic significance of this biomarker in the rituximab era.

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Figures

Figure 1.
Figure 1.
(A) Fluorescence in situ hybridization on formalin-fixed, paraffin-embedded tissue sections on a tissue microarray. Left panel: interphase nuclei with BCL6 break apart (BCL6+). The most common signal pattern is one fusion signal (yellow) and two split signals (1 red, 1 green) visualized at 200× magnification. Right panel: BCL6+ interphase nuclei with break apart (split signals) and polyploidy (multiple fused signals) of the BCL6 locus (high power field). (B) Immunohistochemistry for BCL-6 on tissue microarray cores. Left panel: positive staining in virtually all large B cells. Right panel: negative staining.
Figure 2.
Figure 2.
Overall survival according to BCL6 rearrangement status. (A) CHOP-treated patients (n=65). (B) R-CHOP-treated patients (n=99).
See this image and copyright information in PMC

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