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Published on: March 30, 2018
Longer failure-free survival interval of Epstein-Barr virus-associated classical Hodgkin's lymphoma: a
Jens Krugmann1, Alexandar Tzankov, Andreas Gschwendtner
1Institute of Pathology, University of Innsbruck, Austria.
Insights
Epstein-Barr virus (EBV) association in classical Hodgkin's lymphoma (cHL) was studied, finding EBV positivity linked to longer failure-free survival. However, EBV did not impact overall survival, and the latent membrane protein1 gene deletion showed no significant clinical effect.
Area of Science:
- Oncology
- Virology
- Pathology
Background:
- Epstein-Barr virus (EBV) is implicated in various lymphomas, including classical Hodgkin's lymphoma (cHL).
- The role of EBV latent membrane protein1 (LMP1) gene configuration in cHL pathogenesis and patient outcomes requires further investigation.
Purpose of the Study:
- To analyze the association of EBV with cHL in a single Austrian center.
- To investigate the impact of EBV latent membrane protein1 (LMP1) gene configuration on clinical outcomes, including failure-free and overall survival.
Main Methods:
- Analysis of 119 cHL patients treated between 1974-1999.
- EBV detection using latent membrane protein1 (LMP1) immunohistochemistry and in situ hybridization for EBV-encoded RNA.
- EBV subtyping and LMP1 gene configuration assessment via polymerase chain reaction (PCR).
- Correlation of EBV status and LMP1 variants with clinical parameters and survival outcomes.
Main Results:
- EBV was detected in 26% of cHL cases.
- EBV-associated cHL showed a significantly longer mean time to first relapse (99 months vs. 49 months, P <.02).
- EBV-positive cHL was more frequent in older patients (>45 years), mixed-cellularity subtype, males, advanced stage (III/IV), and those with B symptoms or risk factors.
- Overall survival did not correlate with EBV association.
- The 30-base pair LMP1 gene deletion was infrequent and had no influence on survival outcomes.
Conclusions:
- EBV positivity in cHL is associated with a longer failure-free survival, despite a higher frequency of adverse clinical factors.
- The prevalence of EBV in cHL in this Western European cohort is relatively low.
- The latent membrane protein1 gene deletion variant does not appear to confer increased oncogenic potential or affect patient survival.
Abstract:
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.
