title: Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium.
abstract: The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols. Optimal cut points predicting overall survival of patients treated in the rituximab era could only be determined for CD5 (P = .003) and Ki67 (P = .02), whereas such cut points for BCL2, BCL6, HLA-DR, and MUM1 could only be defined in patients not receiving rituximab. A prognostic model for patients treated in the rituximab era identified 4 risk groups using BCL2, Ki67, and International Prognostic Index (IPI) with improved discrimination of low-risk patients. Newly recognized correlations between specific biomarkers and IPI highlight the importance of carefully controlling for clinical and biologic factors in prognostic models. These data demonstrate that the IPI remains the best available index in patients with DLBCL treated with rituximab and chemotherapy.
authors.affiliation: Hospices Civils de Lyon and Université Claude Bernard Lyon-1, Lyon, France. gilles.salles@chu-lyon.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Maria
authors.initials: M
authors.lastname: Calaminici
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sander
authors.forename: Christoph
authors.initials: C
authors.lastname: Thorns
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Thierry
authors.initials: T
authors.lastname: Molina
authors.forename: Abigail
authors.initials: A
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Sandra
authors.initials: S
authors.lastname: Horning
authors.forename: Andrew
authors.initials: A
authors.lastname: Lister
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: John
authors.initials: J
authors.lastname: Raemaekers
authors.forename: Anton
authors.initials: A
authors.lastname: Hagenbeek
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005060:Europe; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009656:North America; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D012306:Risk; D000069283:Rituximab; D013223:Statistics as Topic; D016019:Survival Analysis; D046888:Tissue Array Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone