TY - JOUR
T1 - Immunohistochemical prognostic markers in diffuse large B-cell lymphoma
T2 - validation of tissue microarray as a prerequisite for broad clinical applications--a study from the Lunenburg Lymphoma Biomarker Consortium
AU - Lunenburg Lymphoma Biomarker Consortium
AU - de Jong, Daphne
AU - Rosenwald, Andreas
AU - Chhanabhai, Mukesh
AU - Gaulard, Philippe
AU - Klapper, Wolfram
AU - Lee, Abigail
AU - Sander, Birgitta
AU - Thorns, Christoph
AU - Campo, Elias
AU - Molina, Thierry
AU - Norton, Andrew
AU - Hagenbeek, Anton
AU - Horning, Sandra
AU - Lister, Andrew
AU - Raemaekers, John
AU - Gascoyne, Randy D
AU - Salles, Gilles
AU - Weller, Edie
PY - 2007/3/1
Y1 - 2007/3/1
N2 - PURPOSE: The results of immunohistochemical class prediction and prognostic stratification of diffuse large B-cell lymphoma (DLBCL) have been remarkably various thus far. Apart from biologic variations, this may be caused by differences in laboratory techniques, scoring definitions, and inter- and intraobserver variations. In this study, an international collaboration of clinical lymphoma research groups from Europe, United States, and Canada concentrated on validation and standardization of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL.PATIENTS AND METHODS: Sections of a tissue microarray from 36 patients with DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM1, and MIB-1 according to local methods. The study was performed in two rounds firstly focused on the evaluation of laboratory staining variation and secondly on the scoring variation.RESULTS: Different laboratory staining techniques resulted in unexpectedly highly variable results and very poor reproducibility in scoring for almost all markers. No single laboratory stood out as uniformly poor or excellent. With elimination of variation due to staining, high agreement was found for CD20, HLA-DR, and CD10. Poor agreement was found for bcl-6 and Ki-67. Optimization of techniques and uniformly agreed on scoring criteria improved reproducibility.CONCLUSION: This study shows that semiquantitative immunohistochemistry for subclassification of DLBCL is feasible and reproducible, but exhibits varying rates of concordance for different markers. These findings may explain the wide variation of biomarker prognostic impact reported in the literature. Harmonization of techniques and centralized consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.
AB - PURPOSE: The results of immunohistochemical class prediction and prognostic stratification of diffuse large B-cell lymphoma (DLBCL) have been remarkably various thus far. Apart from biologic variations, this may be caused by differences in laboratory techniques, scoring definitions, and inter- and intraobserver variations. In this study, an international collaboration of clinical lymphoma research groups from Europe, United States, and Canada concentrated on validation and standardization of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL.PATIENTS AND METHODS: Sections of a tissue microarray from 36 patients with DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM1, and MIB-1 according to local methods. The study was performed in two rounds firstly focused on the evaluation of laboratory staining variation and secondly on the scoring variation.RESULTS: Different laboratory staining techniques resulted in unexpectedly highly variable results and very poor reproducibility in scoring for almost all markers. No single laboratory stood out as uniformly poor or excellent. With elimination of variation due to staining, high agreement was found for CD20, HLA-DR, and CD10. Poor agreement was found for bcl-6 and Ki-67. Optimization of techniques and uniformly agreed on scoring criteria improved reproducibility.CONCLUSION: This study shows that semiquantitative immunohistochemistry for subclassification of DLBCL is feasible and reproducible, but exhibits varying rates of concordance for different markers. These findings may explain the wide variation of biomarker prognostic impact reported in the literature. Harmonization of techniques and centralized consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.
KW - Biomarkers, Tumor
KW - CD5 Antigens
KW - DNA-Binding Proteins
KW - Humans
KW - Immunohistochemistry
KW - Journal Article
KW - Lymphoma, B-Cell
KW - Lymphoma, Large B-Cell, Diffuse
KW - Neprilysin
KW - Prognosis
KW - Proto-Oncogene Proteins c-bcl-2
KW - Proto-Oncogene Proteins c-bcl-6
KW - Research Support, Non-U.S. Gov't
KW - Tissue Array Analysis
U2 - https://doi.org/10.1200/JCO.2006.09.4490
DO - https://doi.org/10.1200/JCO.2006.09.4490
M3 - Article
C2 - 17327602
SN - 0732-183X
VL - 25
SP - 805
EP - 812
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 7
ER -