Dataset Information

Clinical significance of MYC expression and/or "high-grade" morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study.

ABSTRACT: The clinicopathologic findings in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) may show significant overlap, and MYC abnormalities, found in all BLs, also occur in a subset of DLBCL. The 2008 World Health Organization classification introduced the category of "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (BCLU) in recognition of this overlap, but the clinical significance of BCLU (ie, "high-grade") morphology and the relationship between BCLU morphology and MYC abnormalities remains unclear. In this study, we identified 260 cases of non-Burkitt, diffuse aggressive B-cell lymphomas from SWOG S9704, a phase 3 randomized study of standard immunochemotherapy versus autologous stem cell transplantation. Of these, 31 cases (12%) showed BCLU morphology, and 229 (88%) showed typical DLBCL morphology. Of 198, 27 (14%) were positive for MYC by immunohistochemistry. BCLU morphology was associated with an increased incidence of MYC expression but otherwise was not associated with distinct clinicopathologic features or significantly decreased survival. MYC-positive cases were morphologically and phenotypically heterogenous and were associated with poor progression-free and overall survival in multivariate analysis. These findings confirm that BCLU does not represent a distinct clinicopathologic entity and demonstrate that BCLU morphology alone does not significantly impact survival compared with typical DLBCL. In contrast, MYC protein expression is a poor prognostic factor that may be associated with either BCLU or DLBCL morphology, and MYC immunohistochemistry is suggested for routine prognostic evaluation (Clinicaltrials.gov identifier: NCT00004031).

SUBMITTER: Cook JR

PROVIDER: S-EPMC3955880 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Clinical significance of MYC expression and/or "high-grade" morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study.

Cook James R JR Goldman Bryan B Tubbs Raymond R RR Rimsza Lisa L Leblanc Michael M Stiff Patrick P Fisher Richard R

The American journal of surgical pathology 20140401 4

The clinicopathologic findings in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) may show significant overlap, and MYC abnormalities, found in all BLs, also occur in a subset of DLBCL. The 2008 World Health Organization classification introduced the category of "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (BCLU) in recognition of this overlap, but the clinical significance of BCLU (ie, "high-grade") morphology and the relationship between BC ...[more]

PMID: 24625415

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Project description:Classifiers based on molecular criteria such as gene expression signatures have been developed to distinguish Burkitt lymphoma and diffuse large B cell lymphoma, which help to explore the intermediate cases where traditional diagnosis is difficult. Transfer of these research classifiers into a clinical setting is challenging because there are competing classifiers in the literature based on different methodology and gene sets with no clear best choice; classifiers based on one expression measurement platform may not transfer effectively to another; and, classifiers developed using fresh frozen samples may not work effectively with the commonly used and more convenient formalin fixed paraffin-embedded samples used in routine diagnosis.Here we thoroughly compared two published high profile classifiers developed on data from different Affymetrix array platforms and fresh-frozen tissue, examining their transferability and concordance. Based on this analysis, a new Burkitt and diffuse large B cell lymphoma classifier (BDC) was developed and employed on Illumina DASL data from our own paraffin-embedded samples, allowing comparison with the diagnosis made in a central haematopathology laboratory and evaluation of clinical relevance.We show that both previous classifiers can be recapitulated using very much smaller gene sets than originally employed, and that the classification result is closely dependent on the Burkitt lymphoma criteria applied in the training set. The BDC classification on our data exhibits high agreement (~95 %) with the original diagnosis. A simple outcome comparison in the patients presenting intermediate features on conventional criteria suggests that the cases classified as Burkitt lymphoma by BDC have worse response to standard diffuse large B cell lymphoma treatment than those classified as diffuse large B cell lymphoma.In this study, we comprehensively investigate two previous Burkitt lymphoma molecular classifiers, and implement a new gene expression classifier, BDC, that works effectively on paraffin-embedded samples and provides useful information for treatment decisions. The classifier is available as a free software package under the GNU public licence within the R statistical software environment through the link http://www.bioinformatics.leeds.ac.uk/labpages/softwares/ or on github https://github.com/Sharlene/BDC.

Dataset Information

Clinical significance of MYC expression and/or "high-grade" morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study.

Publications

Clinical significance of MYC expression and/or "high-grade" morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study.

Similar Datasets

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