title: Different biological risk factors in young poor-prognosis and elderly patients with diffuse large B-cell lymphoma.
abstract: Prognostically relevant risk factors in patients with diffuse large B-cell lymphoma (DLBCL) have predominantly been evaluated in elderly populations. We tested whether previously described risk factors are also valid in younger, poor-prognosis DLBCL patients. Paraffin-embedded samples from 112 patients with de novo DLBCL, enrolled in the R-MegaCHOEP trial of the German High Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) were investigated using immunohistochemistry (MYC, FOXP1, LMO2, GCET1, CD5, CD10, BCL2, BCL6, IRF4/MUM1) and fluorescence in situ hybridization (MYC, BCL2, BCL6). MYC, BCL2 and BCL6 breaks occurred in 14, 21 and 31%, respectively. In the majority of cases, MYC was simultaneously rearranged with BCL2 and/or BCL6. The adverse impact of MYC rearrangements was confirmed, but the sole presence of BCL2 breaks emerged as a novel prognostic marker associated with inferior overall survival (OS) (P=0.002). Combined overexpression of MYC and BCL2 showed only limited association with inferior OS. All immunohistochemical cell of origin classifiers applied failed to predict survival time. DLBCL tumors with significant proportion of immunoblastic and/or immunoblastic-plasmacytoid cells had inferior OS, independently from from BCL2 break. Younger, poor-prognosis DLBCL patients, therefore, display different biological risk factors compared with an elderly population, with BCL2 translocations emerging as a powerful negative prognostic marker.
authors: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tuebingen, Stuttgart, Germany.
authors: H
authors: H
authors: Horn
authors: Institute for Medical Informatics, Statistics and Epidemiology, Universität Leipzig, Leipzig, Germany.
authors: M
authors: M
authors: Ziepert
authors: Institute of Pathology, Universität Würzburg and Comprehensive Cancer Center Mainfranken (CCCMF), Würzburg, Germany.
authors: M
authors: M
authors: Wartenberg
authors: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tuebingen, Stuttgart, Germany.
authors: A M
authors: AM
authors: Staiger
authors: Institute of Pathology, Universitätsklinikum Ulm, Ulm, Germany.
authors: T F E
authors: TF
authors: Barth
authors: Institute of Pathology, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
authors: H-W
authors: HW
authors: Bernd
authors: Institute of Pathology, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
authors: A C
authors: AC
authors: Feller
authors: Institute of Pathology, Hematopathology Section and Lymph Node Registry, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: W
authors: W
authors: Klapper
authors: Institute of Pathology, Hematopathology Section and Lymph Node Registry, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: C
authors: C
authors: Stuhlmann-Laeisz
authors: Institute of Pathology, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Germany.
authors: M
authors: M
authors: Hummel
authors: Pathodiagnostik Berlin, Berlin, Germany.
authors: H
authors: H
authors: Stein
authors: Institute of Pathology, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Germany.
authors: D
authors: D
authors: Lenze
authors: Institute of Pathology, Universitätsklinikum Frankfurt, Frankfurt, Germany.
authors: S
authors: S
authors: Hartmann
authors: Institute of Pathology, Universitätsklinikum Frankfurt, Frankfurt, Germany.
authors: M-L
authors: ML
authors: Hansmann
authors: Institute of Pathology, Universitätsklinikum Ulm, Ulm, Germany.
authors: P
authors: P
authors: Möller
authors: Institute of Pathology, Kantonal Hospital St Gallen, St Gallen, Switzerland.
authors: S
authors: S
authors: Cogliatti
authors: Medizinische Klinik I, Saarland University Medical School, Homburg/Saar, Germany.
authors: M
authors: M
authors: Pfreundschuh
authors: Department of Hematology and Oncology, Georg-August Universität, Göttingen, Germany.
authors: L
authors: L
authors: Trümper
authors: Institute for Medical Informatics, Statistics and Epidemiology, Universität Leipzig, Leipzig, Germany.
authors: M
authors: M
authors: Loeffler
authors: Department of Hematology, Asklepios Klinik St Georg, Hamburg, Germany.
authors: B
authors: B
authors: Glass
authors: Department of Hematology, Asklepios Klinik St Georg, Hamburg, Germany.
authors: N
authors: N
authors: Schmitz
authors: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
authors: G
authors: G
authors: Ott
authors: Institute of Pathology, Universität Würzburg and Comprehensive Cancer Center Mainfranken (CCCMF), Würzburg, Germany.
authors: A
authors: A
authors: Rosenwald
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc