title: Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP.
abstract: Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high- and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell lymphoma patients treated uniformly with R-CHOP. When the modified classification using MUM1/IRF4 and FOXP1 positivities as activated B-cell-like markers was applied to distinguish the patients between the activated B-cell-like and other diffuse large B-cell lymphoma subtypes, a significantly worse outcome was seen for the patients with the activated B-cell-like phenotype (3-year failure-free survival 63 vs 82%, P=0.048, overall survival 69 vs 85%, P=0.110). Similarly, according to the Muris algorithm, the group 2 patients representing Bcl-2-positive post-germinal center patients showed an inferior outcome in comparison to the group 1 patients (failure-free survival 59 vs 81%, P=0.041, overall survival 67 vs 82%, P=0.159). In contrast, when the classification of the same cohort was performed according to the Hans algorithm, no significant difference in survival was observed between the germinal center and non-germinal center patients. In conclusion, the data suggest that both the modified activated B-cell-like and Muris classifications define the non-germinal center phenotype as an adverse risk factor in R-CHOP-treated diffuse large B-cell lymphoma patients.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. heidi.nyman@helsinki.fi
authors.forename: Heidi
authors.initials: H
authors.lastname: Nyman
authors.forename: Mats
authors.initials: M
authors.lastname: Jerkeman
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Karjalainen-Lindsberg
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Sirpa
authors.initials: S
authors.lastname: Leppä
mesh_terms: D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D003520:Cyclophosphamide / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004317:Doxorubicin / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000276:immunology* / Q000473:pathology*; D015260:Neprilysin / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D000069283:Rituximab; D014750:Vincristine / Q000627:therapeutic use; D000099218:Interferon Regulatory Factor-4
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D051858:Forkhead Transcription Factors; D050835:Interferon Regulatory Factors; D015260:Neprilysin; D011239:Prednisolone; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D000069283:Rituximab; D014750:Vincristine; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C486626:FOXP1 protein, human