This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Montalbán, C. Articles by Piris, M. A. Search for Related Content PubMed PubMed Citation Articles by Montalbán, C. Articles by Piris, M. A.

Influence of Biologic Markers on the Outcome of Hodgkin's Lymphoma: A Study by the Spanish Hodgkin’s Lymphoma Study Group

From the Medicina Interna, Hematología, and Unidad de Bioestadística Clínica, Hospital Ramón y Cajal; Lymphoma Group, Molecular Pathology Program, Centro Nacional de Investigaciones Oncológicas; Hospital Universitario 12 de Octubre; Hospital Clínico Universitario San Carlos; Hospital General Universitario Gregorio Marañón; Hospital de Móstoles, Madrid; Hospital Clínico Universitario, Santiago de Compostela; Hospital Marqués de Valdecilla, Santander; Hospital Virgen de la Salud, Toledo; Hospital Clínico Universitario, Salamanca; Hospital Universitario de Canarias, Tenerife; Complejo Hospitalario Xeral-Cies, Vigo; Hospital Central de Asturias, Oviedo; and Hospital Severo Ochoa, Leganés, Spain.

Address reprint requests to Juan F. García, MD, PhD, Molecular Pathology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), C/O Melchor Fernández Almagro, 3 E-28029 Madrid, Spain; e-mai: jfgarcia{at}cnio.es

PURPOSE: Current therapies fail to cure a significant proportion of patients with Hodgkin's lymphoma (HL). Predictive systems for stratification of the disease and selection of treatment based on sets of clinical variables, such as the international prognostic score (IPS), are of relatively small practical value. The predictive use of biologic parameters has so far provided limited and inconsistent results. Here we explore the influence of a set of molecular markers on the outcome of HL.

PATIENTS AND METHODS: Forty molecular markers involved in B-cell differentiation and activation, signal transduction, cell cycle, and apoptosis control were analyzed in 259 classic HL patient cases by using tissue microarrays. Univariate analysis was performed to evaluate the influence of markers on favorable outcome (complete remission of > 12 months). Significant variables were included in a multivariate logistic regression analysis, and the probability of favorable outcome was estimated.

RESULTS: Univariate analysis revealed four molecular markers that predicted outcome, and the multivariate analysis showed p53, Bcl-X_L, and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) to have independent significance. The combination of these factors determined two groups of patients (group I, zero to one factor; group II, two to three factors) with a probability of a favorable outcome of .948 and .687, respectively. A multivariate Cox's model shows that these biologic risk groups have special predictive power in low-IPS patients.

CONCLUSION: The data from this exploratory study suggest that the accumulation of molecular events seems to influence the outcome of HL, particularly in the low-IPS group.

Supported by grants from the Fondo de Investigaciones Sanitarias (FIS PI020323 and G03/179) and the Ministerio de Ciencia y Tecnología (SAF2001-0060), Spain.

Carlos Montalbán and Juan F. García contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

This article has been cited by other articles:

				I. A. Doussis-Anagnostopoulou, T. P. Vassilakopoulos, I. Thymara, P. Korkolopoulou, M. K. Angelopoulou, M. P. Siakantaris, S. I. Kokoris, E. M. Dimitriadou, C. Kalpadakis, M. Matzouranis, et al. Topoisomerase II{alpha} Expression as an Independent Prognostic Factor in Hodgkin's Lymphoma Clin. Cancer Res., March 15, 2008; 14(6): 1759 - 1766. [Abstract] [Full Text] [PDF]

				T. Alvaro, M. Lejeune, J. F. Garcia, Ma. T. Salvado, C. Lopez, R. Bosch, J. Jaen, P. Escriva, and L. E. Pons Tumor-Infiltrated Immune Response Correlates with Alterations in the Apoptotic and Cell Cycle Pathways in Hodgkin and Reed-Sternberg Cells Clin. Cancer Res., February 1, 2008; 14(3): 685 - 691. [Abstract] [Full Text] [PDF]

				S. Valsami, V. Pappa, D. Rontogianni, F. Kontsioti, E. Papageorgiou, J. Dervenoulas, T. Karmiris, S. Papageorgiou, N. Harhalakis, N. Xiros, et al. A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin's lymphoma: a potential prognostic role of MUM1/IRF4 Haematologica, October 1, 2007; 92(10): 1343 - 1350. [Abstract] [Full Text] [PDF]

				A. Sanchez-Aguilera, C. Montalban, P. de la Cueva, L. Sanchez-Verde, M. M. Morente, M. Garcia-Cosio, J. Garcia-Larana, C. Bellas, M. Provencio, V. Romagosa, et al. Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma Blood, July 15, 2006; 108(2): 662 - 668. [Abstract] [Full Text] [PDF]

				S. J. Sup, C. A. Alemany, B. Pohlman, P. Elson, S. Malhi, S. Thakkar, R. Steinle, and E. D. Hsi Expression of bcl-2 in Classical Hodgkin's Lymphoma: An Independent Predictor of Poor Outcome J. Clin. Oncol., June 1, 2005; 23(16): 3773 - 3779. [Abstract] [Full Text] [PDF]

				N. Spector, C. B. Milito, I. Biasoli, and J. C. Morais p53 Expression As a Prognostic Indicator in Hodgkin's Lymphoma J. Clin. Oncol., May 1, 2005; 23(13): 3158 - 3159. [Full Text] [PDF]

				J. F. Garcia In Reply: J. Clin. Oncol., May 1, 2005; 23(13): 3159 - 3160. [Full Text] [PDF]

				T. Alvaro, M. Lejeune, M. T. Salvado, R. Bosch, J. F. Garcia, J. Jaen, A. H. Banham, G. Roncador, C. Montalban, and M. A. Piris Outcome in Hodgkin's Lymphoma Can Be Predicted from the Presence of Accompanying Cytotoxic and Regulatory T Cells Clin. Cancer Res., February 15, 2005; 11(4): 1467 - 1473. [Abstract] [Full Text] [PDF]