title: 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: BACKGROUND
  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.
  
  
  METHODS
  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.affiliation: Department of Pathology, University of Arizona, Tucson, AZ, USA. cfhaarer@mac.com
authors.forename: Chadwick F
authors.initials: CF
authors.lastname: Haarer
authors.forename: Robin A
authors.initials: RA
authors.lastname: Roberts
authors.forename: Yvette M
authors.initials: YM
authors.lastname: Frutiger
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000145:classification; D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D050835:Interferon Regulatory Factors / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000145:classification* / Q000235:genetics / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000235:genetics / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D015203:Reproducibility of Results; D015996:Survival Rate; D046888:Tissue Array Analysis; D000099218:Interferon Regulatory Factor-4
chemical_list: D014408:Biomarkers, Tumor; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4