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

Arch Pathol Lab Med. 2006 Dec;130(12):1819-24. doi: 10.5858/2006-130-1819-ICODNT.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

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