Longer failure-free survival interval of Epstein-Barr virus-associated classical Hodgkin's lymphoma: a single-institution study

Jens Krugmann, Alexandar Tzankov, Andreas Gschwendtner, Martina Fischhofer, Richard Greil, Falko Fend, Stephan Dirnhofer
Modern Pathology 2003, 16 (6): 566-73
We analyzed Epstein-Barr virus association in classical Hodgkin's lymphoma from a single center in Austria with special emphasis on the latent membrane protein1 gene configuration and clinical outcome. All 119 (65 male, 54 female) patients were treated from 1974 to 1999 in the Division of Hematology and Oncology at the Department of Internal Medicine, University of Innsbruck, Austria. The mean follow-up time was 122 months (range, 3-333 mo). Epstein-Barr virus was examined by latent membrane protein1 immunohistochemistry and by in situ hybridization for Epstein-Barr virus-encoded early ribonuclein acid transcripts. For assessment of the Epstein-Barr virus subtype (A/B) and latent membrane protein1 gene configuration, the polymerase chain reaction was employed. Fifty-four reactive tonsils were used as the control population. These results as well as clinical parameters such as age, gender, tumor stage, risk factors, and B symptoms were correlated with failure-free and overall survival. Latent membrane protein1 was detected in 31/119 (26%) classical Hodgkin's lymphoma, and Epstein-Barr virus subtyping was successful in 19 of the 31 virus-infected classical Hodgkin's lymphoma cases, as well as in 28 of 54 reactive tonsils. Subtype A was observed in all classical Hodgkin's lymphoma patients and in 26/28 (93%) tonsils. The 30-base pair latent membrane protein1 gene deletion was found in only 4/31 (13%) Epstein-Barr virus-associated classical Hodgkin's lymphoma as well as in 20/54 (37%) reactive tonsils. Patients with Epstein-Barr virus-associated classical Hodgkin's lymphoma showed a significantly longer mean time to first relapse of 99 months, as compared with 49 months for the Epstein-Barr virus-negative cases (P <.02), and were more frequent in those aged >45 years (P <.04). Epstein-Barr virus-associated classical Hodgkin's lymphoma were predominantly of the mixed-cellularity subtype and occurred more frequently in male patients, in patients with Stage III and IV, and in patients with B symptoms as well as risk factors. However, overall survival did not correlate with Epstein-Barr virus association. The 30-base pair latent membrane protein1 gene deletion had no influence on overall survival and failure-free survival time. Although the number of patients with this specific mutation was low, it further shows that an increased oncogenic potential of the latent membrane protein1 deletion variant is unlikely. This large single-center study demonstrates a low prevalence of Epstein-Barr virus positivity in classical Hodgkin's lymphoma in western Europe. In accordance with results of similar studies, the presence of Epstein-Barr virus has a beneficial effect on the length of failure-free survival despite the higher frequency of risk factors such as higher tumor stage or advanced age.

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