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Adverse Clinical Outcome in Hodgkin's Disease Is Associated With Loss of Retinoblastoma Protein Expression, High Ki67 Proliferation Index, and Absence of Epstein-Barr Virus-Latent Membrane Protein 1 Expression
Manuel M. Morente,
Miguel A. Piris,
Victor Abraira,
Agustin Acevedo,
Beatriz Aguilera,
Carmen Bellas,
Máximo Fraga,
Raimundo Garcia-Del-Moral,
Francisco Gomez-Marcos,
Javier Menarguez,
Horacio Oliva,
Margarita Sanchez-Beato, and
Carlos Montalban
From the Department of Pathology, Hospital General Universitario, Universidad de Alcalá, Guadalajara; Department of Pathology, Hospital Virgen de la Salud, Toledo; Clinical Epidemiology and Biostatistics Unit, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid; Department of Pathology, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid; Department of Pathology, Instituto Nacional de Toxicologia, Madrid; Department of Pathology, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid; Department of Pathology, Hospital General de Galicia, Universidad de Santiago de Compostela, Santiago de Compostela; Department of Pathology, Hospital Clinico San Cecilio, Universidad de Granada, Granada; Department of Pathology, Hospital Gregorio Marañón, Universidad Complutense, Madrid; Department of Pathology, Fundación Jimenez Diaz, Universidad Autónoma de Madrid, Madrid; and Department of Internal Medicine, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
Previous studies have shown that in non-Hodgkin's lymphomas and others neoplasms, tumoral progression, treatment response, and outcome are related to the expression of different oncogenic and tumor suppressor proteins. This study aimed to determine the prognostic significance of the expression of p53, bcl2, retinoblastoma protein (Rb), Ki67, CD15, and latent membrane protein 1-Epstein-Barr Virus (LMP1-EBV) proteins in Hodgkin's disease. A retrospective study was performed on 140 patients collected at the 11 participating centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. A highly sensitive immunohistochemical method with previous microwave-induced antigen retrieval technique was used for the demonstration of the above-mentioned proteins. A Cox's multivariate analysis was performed to evaluate the impact of the variables in the overall survival, together with a logistic regression model for the achievement of complete remission. Univariate statistical analysis confirmed the prognostic significance of the alredy known clinical parameters: stage, age over 60 years, and B symptoms. High proliferation index (Ki67) and loss of Rb expression were also found to be adverse prognostic factors influencing respectively lower overall survival and failure to achieve complete remission. Multivariate analysis confirmed the independent significance of these two parameters and additionally identifies LMP1-EBV expression as a favorable prognostic marker, in relation with overall survival. Histopathological type, p53, bcl2, and CD15 expression lack significant influence on the outcome of this series. The progression of the disease or the response to treatment in HD patients is the consequence of the interrelationship of different factors, among which LMP1 expression, loss of Rb, and high growth fraction seems to play a more relevant role.
Blood, Vol. 90 No. 6 (September 15), 1997:
pp. 2429-2436
© 1997 by The American Society of Hematology.
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