Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium

Gilles Salles; Daphne de Jong; Wanling Xie; Andreas Rosenwald; Mukesh Chhanabhai; Philippe Gaulard; Wolfram Klapper; Maria Calaminici; Birgitta Sander; Christoph Thorns; Elias Campo; Thierry Molina; Abigail Lee; Michael Pfreundschuh; Sandra Horning; Andrew Lister; Laurie H Sehn; John Raemaekers; Anton Hagenbeek; Randy D Gascoyne; Edie Weller

doi:https://doi.org/10.1182/blood-2011-04-345256

Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium

Gilles Salles, Daphne de Jong, Wanling Xie, Andreas Rosenwald, Mukesh Chhanabhai, Philippe Gaulard, Wolfram Klapper, Maria Calaminici, Birgitta Sander, Christoph Thorns, Elias Campo, Thierry Molina, Abigail Lee, Michael Pfreundschuh, Sandra Horning, Andrew Lister, Laurie H Sehn, John Raemaekers, Anton Hagenbeek, Randy D GascoyneEdie Weller

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	7070-8
Number of pages	9
Journal	Blood
Volume	117
Issue number	26
DOIs	https://doi.org/10.1182/blood-2011-04-345256
Publication status	Published - 30 Jun 2011

Keywords

Aged
Antibodies, Monoclonal, Murine-Derived
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Cohort Studies
Cyclophosphamide
Doxorubicin
Europe
Humans
Immunohistochemistry
Journal Article
Lymphoma, Large B-Cell, Diffuse
Middle Aged
North America
Prednisone
Prognosis
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Risk
Rituximab
Statistics as Topic
Survival Analysis
Tissue Array Analysis
Vincristine

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https://doi.org/10.1182/blood-2011-04-345256

Cite this

Salles, G., de Jong, D., Xie, W., Rosenwald, A., Chhanabhai, M., Gaulard, P., Klapper, W., Calaminici, M., Sander, B., Thorns, C., Campo, E., Molina, T., Lee, A., Pfreundschuh, M., Horning, S., Lister, A., Sehn, L. H., Raemaekers, J., Hagenbeek, A., ... Weller, E. (2011). Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium. Blood, 117(26), 7070-8. https://doi.org/10.1182/blood-2011-04-345256

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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.",

keywords = "Aged, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Cohort Studies, Cyclophosphamide, Doxorubicin, Europe, Humans, Immunohistochemistry, Journal Article, Lymphoma, Large B-Cell, Diffuse, Middle Aged, North America, Prednisone, Prognosis, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Risk, Rituximab, Statistics as Topic, Survival Analysis, Tissue Array Analysis, Vincristine",

author = "Gilles Salles and {de Jong}, Daphne and Wanling Xie and Andreas Rosenwald and Mukesh Chhanabhai and Philippe Gaulard and Wolfram Klapper and Maria Calaminici and Birgitta Sander and Christoph Thorns and Elias Campo and Thierry Molina and Abigail Lee and Michael Pfreundschuh and Sandra Horning and Andrew Lister and Sehn, {Laurie H} and John Raemaekers and Anton Hagenbeek and Gascoyne, {Randy D} and Edie Weller",

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Salles, G, de Jong, D, Xie, W, Rosenwald, A, Chhanabhai, M, Gaulard, P, Klapper, W, Calaminici, M, Sander, B, Thorns, C, Campo, E, Molina, T, Lee, A, Pfreundschuh, M, Horning, S, Lister, A, Sehn, LH, Raemaekers, J, Hagenbeek, A, Gascoyne, RD & Weller, E 2011, 'Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium', Blood, vol. 117, no. 26, pp. 7070-8. https://doi.org/10.1182/blood-2011-04-345256

TY - JOUR

T1 - Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma

T2 - a study from the Lunenburg Lymphoma Biomarker Consortium

AU - Salles, Gilles

AU - de Jong, Daphne

AU - Xie, Wanling

AU - Rosenwald, Andreas

AU - Chhanabhai, Mukesh

AU - Gaulard, Philippe

AU - Klapper, Wolfram

AU - Calaminici, Maria

AU - Sander, Birgitta

AU - Thorns, Christoph

AU - Campo, Elias

AU - Molina, Thierry

AU - Lee, Abigail

AU - Pfreundschuh, Michael

AU - Horning, Sandra

AU - Lister, Andrew

AU - Sehn, Laurie H

AU - Raemaekers, John

AU - Hagenbeek, Anton

AU - Gascoyne, Randy D

AU - Weller, Edie

PY - 2011/6/30

Y1 - 2011/6/30

N2 - 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.

AB - 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.

KW - Aged

KW - Antibodies, Monoclonal, Murine-Derived

KW - Antineoplastic Agents

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Biomarkers, Tumor

KW - Cohort Studies

KW - Cyclophosphamide

KW - Doxorubicin

KW - Europe

KW - Humans

KW - Immunohistochemistry

KW - Journal Article

KW - Lymphoma, Large B-Cell, Diffuse

KW - Middle Aged

KW - North America

KW - Prednisone

KW - Prognosis

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

KW - Risk

KW - Rituximab

KW - Statistics as Topic

KW - Survival Analysis

KW - Tissue Array Analysis

KW - Vincristine

U2 - https://doi.org/10.1182/blood-2011-04-345256

DO - https://doi.org/10.1182/blood-2011-04-345256

M3 - Article

C2 - 21536860

SN - 0006-4971

VL - 117

SP - 7070

EP - 7078

JO - Blood

JF - Blood

IS - 26

ER -