Scientific publications
A molecular risk score based on 4 functional pathways for advanced classical Hodgkin lymphoma
Beatriz Sánchez-Espiridión 1 , Carlos Montalbán, Angel López, Javier Menárguez, Pilar Sabín, Carmen Ruiz-Marcellán, Andrés Lopez, Rafael Ramos, Jose Rodríguez, Araceli Cánovas, Carmen Camarero, Miguel Canales, Javier Alves, Reyes Arranz, Agustín Acevedo, Antonio Salar, Sergio Serrano, Agueda Bas, Jose M Moraleda, Pedro Sánchez-Godoy, Fernando Burgos, Concepción Rayón, Manuel F Fresno, José García Laraña, Mónica García-Cosío, Carlos Santonja, Jose L López, Marta Llanos, Manuela Mollejo, Joaquín González-Carrero, Ana Marín, Jerónimo Forteza, Ramón García-Sanz, Jose F Tomás, Manuel M Morente, Miguel A Piris, Juan F García, Spanish Hodgkin Lymphoma Study Group
Abstract
Despite improvement in the treatment of advanced classical Hodgkin lymphoma, approximately 30% of patients relapse or die as result of the disease.
Current predictive systems, determined by clinical and analytical parameters, fail to identify these high-risk patients accurately. We took a multistep approach to design a quantitative reverse-transcription polymerase chain reaction assay to be applied to routine formalin-fixed paraffin-embedded samples, integrating genes expressed by the tumor cells and their microenvironment.
The significance of 30 genes chosen on the basis of previously published data was evaluated in 282 samples (divided into estimation and validation sets) to build a molecular risk score to predict failure. Adequate reverse-transcription polymerase chain reaction profiles were obtained from 262 of 282 cases (92.9%).
Best predictor genes were integrated into an 11-gene model, including 4 functional pathways (cell cycle, apoptosis, macrophage activation, and interferon regulatory factor 4) able to identify low- and high-risk patients with different rates of 5-year failure-free survival: 74% versus 44.1% in the estimation set (P < .001) and 67.5% versus 45.0% in the validation set (P = .022).
This model can be combined with stage IV into a final predictive model able to identify a group of patients with very bad outcome (5-year failure-free survival probability, 25.2%).
CITATION Blood. 2010 Aug 26;116(8):e12-7. doi: 10.1182/blood-2010-02-270009. Epub 2010 May 17.
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