@article{Birgitta Sander_Daphne de Jong_Andreas Rosenwald_Wanling Xie_Olga Balagué_Maria Calaminici_Joaquim Carreras_Philippe Gaulard_John Gribben_Anton Hagenbeek_Marie José Kersten_Thierry Jo Molina_Abigail Lee_Santiago Montes-Moreno_German Ott_John Raemaekers_Gilles Salles_Laurie Sehn_Christoph Thorns_Björn E. Wahlin_Randy D. Gascoyne_Edie Weller_2014, place={Pavia, Italy}, title={The reliability of immunohistochemical analysis of the tumor microenvironment in follicular lymphoma: a validation study from the Lunenburg Lymphoma Biomarker Consortium}, volume={99}, url={https://haematologica.org/article/view/7002}, DOI={10.3324/haematol.2013.095257}, abstractNote={The cellular microenvironment in follicular lymphoma is of biological and clinical importance. Studies on the clinical significance of non-malignant cell populations have generated conflicting results, which may partly be influenced by poor reproducibility in immunohistochemical marker quantification. In this study, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated. The agreement between manual scoring and flow cytometry was moderate for CD3, low for CD4, and moderate to high for CD8, with some laboratories scoring closer to the flow cytometry results. Agreement in manual quantification across the 7 laboratories was low to moderate for CD3, CD4, CD8 and FOXP3 frequencies, moderate for CD21, low for MIB1 and CD68, and high for CD10. Manual scoring of the architectural distribution resulted in moderate agreement for CD3, CD4 and CD8, and low agreement for FOXP3 and CD68. Comparing manual scoring to automated microscopy demonstrated that manual scoring increased the variability in the low and high frequency interval with some laboratories showing a better agreement with automated scores. Manual scoring reliably identified rare architectural patterns of T-cell infiltrates. Automated microscopy analyses for T-cell markers by two different instruments were highly reproducible and provided acceptable agreement with flow cytometry. These validation results provide explanations for the heterogeneous findings on the prognostic value of the microenvironment in follicular lymphoma. We recommend a more objective measurement, such as computer-assisted scoring, in future studies of the prognostic impact of microenvironment in follicular lymphoma patients.}, number={4}, journal={Haematologica}, author={Birgitta Sander and Daphne de Jong and Andreas Rosenwald and Wanling Xie and Olga Balagué and Maria Calaminici and Joaquim Carreras and Philippe Gaulard and John Gribben and Anton Hagenbeek and Marie José Kersten and Thierry Jo Molina and Abigail Lee and Santiago Montes-Moreno and German Ott and John Raemaekers and Gilles Salles and Laurie Sehn and Christoph Thorns and Björn E. Wahlin and Randy D. Gascoyne and Edie Weller}, year={2014}, month={Mar.}, pages={715-725} }