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Blood, 15 July 2006, Vol. 108, No. 2, pp. 662-668.
Prepublished online as a Blood First Edition Paper on March 21, 2006; DOI 10.1182/blood-2005-12-5125.
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NEOPLASIA
Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma
Abel Sánchez-Aguilera,
Carlos Montalbán,
Paloma de la Cueva,
Lydia Sánchez-Verde,
Manuel M. Morente,
Mónica García-Cosío,
José García-Laraña,
Carmen Bellas,
Mariano Provencio,
Vicens Romagosa,
Alberto Fernández de Sevilla,
Javier Menárguez,
Pilar Sabín,
María J. Mestre,
Miguel Méndez,
Manuel F. Fresno,
Concepción Nicolás,
Miguel A. Piris,
Juan F. García, for the Spanish Hodgkin Lymphoma Study Group
From the Lymphoma Group; the Tumor Bank Network and the Histology and Immunohistochemistry Unit, Spanish National Cancer Centre (CNIO), Madrid; Departments of Internal Medicine, Pathology, and Hematology, Hospital Ramón y Cajal, Madrid; Departments of Pathology and Oncology, Hospital Puerta de Hierro, Madrid; Departments of Pathology and Hematology, Institut Catala d'Oncologia, Barcelona; Departments of Pathology and Oncology, Hospital General Universitario Gregorio Marañón, Madrid; Departments of Pathology and Oncology, Hospital de Móstoles, Madrid; Departments of Pathology and Hematology, Hospital Central de Asturias, Oviedo; and Department of Pathology, M. D. Anderson International, Madrid, Spain.
Around 20% to 30% of patients with Hodgkin lymphoma (HL) do not benefit from standard therapies and finally succumb to their disease. The factors that influence the outcome of HL have not been elucidated, underscoring the demand for the identification of biologic risk factors and new therapeutic targets. We analyzed the gene expression profiles of samples from 29 patients with advanced classic HL treated with standard therapy and compared the expression profiles of patients with favorable and unfavorable clinical outcome. Using supervised methods, we identified 145 genes associated with outcome, which were grouped into 4 signatures representing genes expressed by either the tumoral cells (genes involved in the regulation of mitosis and cell growth/apoptosis) or the tumor microenvironment. The relationship between the expression of 8 representative genes and survival was successfully validated in an independent series of 235 patients by quantification of protein expression levels on tissue microarrays. Analysis of centrosomes and mitotic checkpoint confirmed the existence of an abnormal transition through mitosis in HL cells. Therefore, genes related to tumor microenvironment, cell growth/apoptosis, and regulation of mitosis are associated with treatment response and outcome of patients with HL.
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