title: BCL2 positive and BCL6 negative diffuse large B cell lymphoma patients benefit from R-CHOP therapy irrespective of germinal and non germinal center B cell like subtypes.
abstract: OBJECTIVE
  Despite major advances in the treatment of diffuse large B cell lymphoma (DLBCL), approximately one third of the patients progress or die, suggesting the existence of additional oncogenic events. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. Furthermore, we tried to correlate these parameters with the International Prognostic Index (IPI).
  
  
  METHODS
  The immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin-embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed. IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and BCL2 gene alterations was performed on 67 samples using the tissue microarray (TMA) method.
  
  
  RESULTS
  The Hans algorithm was not predictive of survival in both therapy groups. No significant difference in BCL2 and MYC alterations or MYC protein expression in relation to complete response (CR), event-free survival (EFS) and overall survival (OS) was observed in our study. High IPI correlated significantly with poor outcome and it was identified as independent prognostic factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%, p=0.001) cases.
  
  
  CONCLUSIONS
  IPI is an independent prognosticator for DL-BCL patients and the addition of rituximab significantly improved survival. Furthermore, patients with BCL2+ and BCL6-DLBCL benefited from R-CHOP.
authors.affiliation: Department of Pathology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Maja Perunicic
authors.initials: MP
authors.lastname: Jovanovic
authors.forename: Biljana
authors.initials: B
authors.lastname: Mihaljevic
authors.forename: Ljubomir
authors.initials: L
authors.lastname: Jakovic
authors.forename: Vesna Cemerikic
authors.initials: VC
authors.lastname: Martinovic
authors.forename: Marija Dencic
authors.initials: MD
authors.lastname: Fekete
authors.forename: Bosko
authors.initials: B
authors.lastname: Andjelic
authors.forename: Darko
authors.initials: D
authors.lastname: Antic
authors.forename: Andrija
authors.initials: A
authors.lastname: Bogdanovic
authors.forename: Novica
authors.initials: N
authors.lastname: Boricic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Terzic
authors.forename: Jelena
authors.initials: J
authors.lastname: Jelicic
authors.forename: Sanja
authors.initials: S
authors.lastname: Milenkovic
mesh_terms: D000465:Algorithms; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000032:analysis*; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C000595707:BCL2 protein, human; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone