Immunohistochemical classification of de novo, transformed, and relapsed diffuse large B-cell lymphoma into germinal center B-cell and nongerminal center B-cell subtypes correlates with gene expression profile and patient survival.

Abstract

CONTEXT:

Diffuse large B-cell lymphoma (DLBCL) can be assigned to prognostic subgroups, including germinal center B-cell (GCB) and activated B-cell subgroups, by using gene expression profiling and, reportedly, immunohistochemistry for CD10, Bcl-6, and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4).

OBJECTIVE:

To compare 2 commercial MUM1/IRF4 antibody formulations for accuracy in subtyping DLBCL against gene expression profiling, compare subtyping to patient survival, and evaluate the usefulness of GCB and non-GCB subtyping in relapsed and transformed DLBCL.

DESIGN:

Evaluation of 2 commercial MUM1/IRF4 antibodies, ICSTAT/M17 and Mum-1p, by using 40 cases of de novo, relapsed, and transformed DLBCL; and comparison of the results obtained with gene expression profiling and survival.

RESULTS:

Immunohistochemistry predicted the gene expression profiling subtype 71.8% and 69.2% of the time overall with use of the Mum-1p and ICSTAT/M17 antibodies, respectively, and 100% and 91.7% of the time when MUM1/IRF4 expression determined subtype. Gene expression profiling and immunohistochemistry revealed nearly identical 5-year overall survival rates for the GCB vs non-GCB subtypes (68.0% for GCB vs 24.7% for non-GCB with use of gene expression profiling [P = .03] and 70.2% vs 18.4%, respectively, with use of immunohistochemistry [P < .001]). When de novo, transformed, and relapsed cases were analyzed separately, 5-year overall survival rates were also significantly different.

CONCLUSIONS:

Immunohistochemistry can be used to subclassify DLBCL, including a very small series of transformed and relapsed cases, into GCB and non-GCB subtypes and predict survival rates similar to those predicted by use of gene expression profiling. The 2 MUM1/IRF4 antibodies performed similarly.

• Authors: Chadwick F Haarer, Robin A Roberts, Yvette M Frutiger, Thomas M Grogan, Lisa M Rimsza
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 130 Issue 12 Pg. 1819-24 (Dec 2006) ISSN: 1543-2165 [Electronic] United States
• PMID: 17149956 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• Interferon Regulatory Factors
• interferon regulatory factor-4

Topics

• B-Lymphocytes (pathology)
• Biomarkers, Tumor (analysis, classification)
• Cell Transformation, Neoplastic
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Germinal Center (pathology)
• Humans
• Immunophenotyping
• Interferon Regulatory Factors (analysis)
• Lymphoma, B-Cell (classification, genetics, mortality)
• Lymphoma, Large B-Cell, Diffuse (classification, genetics, mortality)
• Neoplasm Recurrence, Local (mortality, pathology)
• Reproducibility of Results
• Survival Rate
• Tissue Array Analysis