title: A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients.
abstract: OBJECTIVE
  To determine the prognostic significance of co-expression of MYC, BCL-2 and BCL-6 proteins in combination with other biomarkers and clinical characteristics within a population-based cohort of diffuse large B-cell lymphoma (DLBCL) patients uniformly treated with R-CHOP.
  
  
  METHODS
  The immunohistochemical (IHC) expression of CD10, BCL-2, BCL-6, MUM1, MYC, CD5, CD30, Ki-67 and p53 was evaluated in a retrospective, population-based study comprising 188 DLBCL patients treated with R-CHOP and diagnosed in Sweden between 2002 and 2012.
  
  
  RESULTS
  Patients had a median age at diagnosis of 64 years (26-85 years) with a male:female ratio of 1.4:1. Approximately half (52%) of the patients presented with an International Prognostic Index (IPI) age adjusted (IPIaa) ≥ 2. Median follow-up time was 51 months (range 0.4-158) and the five-year lymphoma-specific survival (LSS) was 76%, five-year overall survival (OS) was 65% and five-year progression-free survival (PFS) was 61%. A high Ki-67 value was found in 59% of patients, while p53 overexpression was detected in 12% of patients and MYC, BCL-2 and BCL-6 expression were detected in 42%, 55% and 74% of patients, respectively. IPIaa ≥2 (p = 0.002), Ki-67 ≥ 70% (p = 0.04) and p53 overexpression ≥50% (p = 0.02) were associated with inferior LSS and OS. Co-expression of both MYC (>40%) and BCL-2 (>70%) proteins was detected in 27% of patients and correlated with a significantly inferior LSS (p = 0.0002), OS (p = 0.009) and PFS (p = 0.03). In addition, triple expression of MYC, BCL-2 and BCL-6, also correlated with a significantly inferior LSS (p = 0.02).
  
  
  CONCLUSIONS
  Concurrent expression of MYC and BCL-2 proteins, as detected by IHC, was strongly associated with an inferior survival in DLBCL patients treated with R-CHOP. Other markers affecting survival were triple expression of MYC, BCL-2 and BCL-6, IPIaa, high Ki-67 and p53 overexpression.
authors.affiliation: a Department of Immunology, Genetics and Pathology, Unit of Pathology , Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Maysaa
authors.initials: M
authors.lastname: Abdulla
authors.affiliation: a Department of Immunology, Genetics and Pathology, Unit of Pathology , Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Laszlo
authors.affiliation: b Department of Immunology, Genetics and Pathology, Unit of Oncology , Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Triumf
authors.affiliation: b Department of Immunology, Genetics and Pathology, Unit of Oncology , Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Gustaf
authors.initials: G
authors.lastname: Hedström
authors.affiliation: b Department of Immunology, Genetics and Pathology, Unit of Oncology , Uppsala University and Uppsala University Hospital, Uppsala, Sweden.|c Department of Biosciences and Nutrition , Karolinska Institute, Novum , Huddinge , Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Berglund
authors.affiliation: b Department of Immunology, Genetics and Pathology, Unit of Oncology , Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.affiliation: a Department of Immunology, Genetics and Pathology, Unit of Pathology , Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012189:Retrospective Studies; D000069283:Rituximab; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C000595707:BCL2 protein, human; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; 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; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone