title: Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.
abstract: The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.
authors.affiliation: Department of Oncology, Jubileum Institute, Lund University Hospital, Sweden. mats.jerkeman@onk.lu.se
authors.forename: M
authors.initials: M
authors.lastname: Jerkeman
authors.forename: H
authors.initials: H
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Dictor
authors.forename: S
authors.initials: S
authors.lastname: Kvaløy
authors.forename: M
authors.initials: M
authors.lastname: Akerman
authors.forename: E
authors.initials: E
authors.lastname: Cavallin-Ståhl
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers; D001761:Bleomycin / Q000008:administration & dosage; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D002955:Leucovorin / Q000008:administration & dosage; D015993:Life Tables; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D014411:Neoplastic Stem Cells / Q000737:chemistry; D009664:Norway / Q000453:epidemiology; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012307:Risk Factors; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D001761:Bleomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate