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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2765-3775.
Prepublished online as a Blood First Edition Paper on December 18, 2008; DOI 10.1182/blood-2008-07-168096.


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Submitted July 11, 2008
Accepted November 10, 2008

Molecular profiling of classical Hodgkin's lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome

Bruno Chetaille, Francois Bertucci, Pascal Finetti, Benjamin Esterni, Aspasia Stamatoullas, Jean Michel Picquenot, Marie Christine Copin, Frank Morschhauser, Olivier Casasnovas, Tony Petrella, Thierry Molina, Anne Vekhoff, Pierre Feugier, Reda Bouabdallah, Daniel Birnbaum, Daniel Olive, and Luc Xerri*

Department of Bio-Pathology, Molecular Oncology, Hematology, and Tumor Immunology, Institut Paoli-Calmettes and Universite de la Mediterranee, Marseille, France
Groupe d'Etude des Lymphoproliferations, INSERM U 918, Centre Henri-Becquerel, Rouen, France
Groupe d'Etude des Lymphomes de l'Adulte (GELA), Rouen, France
Department of Pathology and Hematology, Centre Hospitalier and Universite de Lille II, Lille, France
Department of Pathology and Hematology, Centre Hospitalier, Dijon, France
Department of Pathology and Hematology, Hotel-Dieu, Paris, France
Department of Hematology, Centre Hospitalier, Nancy, France

* Corresponding author; email: xerril{at}marseille.fnclcc.fr.

The outcome of classical Hodgkin's lymphoma (cHL) patients may be related to the tumor microenvironment, which in turn may be influenced by EBV infection. To characterize the cHL microenvironment, a set of 63 cHL tissue samples was profiled using DNA microarrays. Their gene expression profile differed from that of T-cell rich B-cell lymphoma (TCRBCL) samples that were used as controls, mainly due to high expression of PDCD1/PD-1 in TCRBCL. EBV+ cHL tissues could be distinguished from EBV- samples by a gene signature characteristic of Th1 and antiviral responses. Samples from cHL patients with favorable outcome overexpressed genes specific of B-cells and genes involved in apoptotic pathways. An independent set of 146 cHL samples was analyzed using immunohistochemistry. It showed a significant adverse value in case of high percentage of either TIA-1+ reactive cells or topoisomerase-2+ tumor cells, whereas high numbers of BCL11A+, FOXP3+ or CD20+ reactive cells had a favorable influence. Immunodetection of BCL11A, a marker of both B-cells and plasmacytoid dendritic cells, had the strongest predictive value. Our results suggest an antitumoral role for B-cells in the cHL microenvironment and a stronger stromal influence of the PD1 pathway in TCRBCL than cHL. The observation of Th1/ anti-viral response in EBV+ cHL tissues provides a basis for novel treatment strategies.


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