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Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP

Nyman, Heidi; Jerkeman, Mats LU ; Karjalainen-Lindsberg, Marja-Liisa; Banham, Alison H. and Leppa, Sirpa (2009) In Modern Pathology 22(8). p.1094-1101
Abstract
Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high-and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell... (More)
Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high-and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell lymphoma patients treated uniformly with R-CHOP. When the modified classification using MUM1/IRF4 and FOXP1 positivities as activated B-cell-like markers was applied to distinguish the patients between the activated B-cell-like and other diffuse large B-cell lymphoma subtypes, a significantly worse outcome was seen for the patients with the activated B-cell-like phenotype (3-year failure-free survival 63 vs 82%, P = 0.048, overall survival 69 vs 85%, P = 0.110). Similarly, according to the Muris algorithm, the group 2 patients representing Bcl-2-positive post-germinal center patients showed an inferior outcome in comparison to the group 1 patients (failure-free survival 59 vs 81%, P = 0.041, overall survival 67 vs 82%, P = 0.159). In contrast, when the classification of the same cohort was performed according to the Hans algorithm, no significant difference in survival was observed between the germinal center and non-germinal center patients. In conclusion, the data suggest that both the modified activated B-cell-like and Muris classifications define the non-germinal center phenotype as an adverse risk factor in R-CHOP-treated diffuse large B-cell lymphoma patients. Modern Pathology (2009) 22, 1094-1101; doi: 10.1038/modpathol.2009.73; published online 15 May 2009 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
prognosis, R-CHOP, activated B-cell-like, diffuse large B-cell lymphoma, MUM1/IRF4
in
Modern Pathology
volume
22
issue
8
pages
1094 - 1101
publisher
Nature Publishing Group
external identifiers
  • wos:000268540400014
  • scopus:68249100654
ISSN
1530-0285
DOI
10.1038/modpathol.2009.73
language
English
LU publication?
yes
id
270c299f-eb8e-499e-a5f8-7094ca78342f (old id 1459861)
date added to LUP
2009-08-31 11:01:02
date last changed
2017-11-05 04:07:11
@article{270c299f-eb8e-499e-a5f8-7094ca78342f,
  abstract     = {Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high-and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell lymphoma patients treated uniformly with R-CHOP. When the modified classification using MUM1/IRF4 and FOXP1 positivities as activated B-cell-like markers was applied to distinguish the patients between the activated B-cell-like and other diffuse large B-cell lymphoma subtypes, a significantly worse outcome was seen for the patients with the activated B-cell-like phenotype (3-year failure-free survival 63 vs 82%, P = 0.048, overall survival 69 vs 85%, P = 0.110). Similarly, according to the Muris algorithm, the group 2 patients representing Bcl-2-positive post-germinal center patients showed an inferior outcome in comparison to the group 1 patients (failure-free survival 59 vs 81%, P = 0.041, overall survival 67 vs 82%, P = 0.159). In contrast, when the classification of the same cohort was performed according to the Hans algorithm, no significant difference in survival was observed between the germinal center and non-germinal center patients. In conclusion, the data suggest that both the modified activated B-cell-like and Muris classifications define the non-germinal center phenotype as an adverse risk factor in R-CHOP-treated diffuse large B-cell lymphoma patients. Modern Pathology (2009) 22, 1094-1101; doi: 10.1038/modpathol.2009.73; published online 15 May 2009},
  author       = {Nyman, Heidi and Jerkeman, Mats and Karjalainen-Lindsberg, Marja-Liisa and Banham, Alison H. and Leppa, Sirpa},
  issn         = {1530-0285},
  keyword      = {prognosis,R-CHOP,activated B-cell-like,diffuse large B-cell lymphoma,MUM1/IRF4},
  language     = {eng},
  number       = {8},
  pages        = {1094--1101},
  publisher    = {Nature Publishing Group},
  series       = {Modern Pathology},
  title        = {Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP},
  url          = {http://dx.doi.org/10.1038/modpathol.2009.73},
  volume       = {22},
  year         = {2009},
}