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Published on: March 30, 2018
The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma
Sarah Park1, Jeeyun Lee, Young Hyeh Ko
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong Kangnam-ku, Seoul 135-710, Korea.
Insights
Epstein-Barr virus (EBV) infection in diffuse large B-cell lymphoma (DLBCL) is linked to poorer survival. EBV-encoded RNA-1 (EBER) positivity indicates a worse prognosis and treatment response in DLBCL patients.
Area of Science:
- Oncology
- Virology
- Pathology
Background:
- Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma.
- The role of Epstein-Barr virus (EBV) in DLBCL pathogenesis and prognosis requires further clarification.
Purpose of the Study:
- To investigate the prognostic impact of EBV infection in DLBCL.
- To determine the association between EBV status and clinical characteristics and outcomes in DLBCL patients.
Main Methods:
- Analysis of 380 DLBCL tissue slides using EBV-encoded RNA-1 (EBER) in situ hybridization.
- Correlation of EBER positivity with clinical factors including age, stage, extranodal involvement, International Prognostic Index (IPI), B symptoms, and treatment response.
Main Results:
- EBV-encoded RNA-1 (EBER) positivity was detected in 9.0% of DLBCL cases.
- EBER positivity significantly correlated with older age, advanced stage, multiple extranodal sites, higher IPI, B symptoms, and poorer initial treatment response.
- EBER-positive DLBCL patients exhibited significantly worse overall survival (OS) and progression-free survival (PFS).
- In the nongerminal center B-cell-like subtype, EBER positivity remained a significant independent predictor of poorer OS, conferring a 2.9-fold increased risk of death.
Conclusions:
- EBV infection, identified by EBER in situ hybridization, is associated with adverse prognostic factors in DLBCL.
- EBV-positive DLBCL patients experience a more aggressive clinical course with inferior survival outcomes.
- EBER status is a valuable prognostic marker, particularly in the nongerminal center B-cell-like subtype of DLBCL.
Abstract:
To define prognostic impact of Epstein-Barr virus (EBV) infection in diffuse large B-cell lymphoma (DLBCL), we investigated EBV status in patients with DLBCL. In all, 380 slides from paraffin-embedded tissue were available for analysis by EBV-encoded RNA-1 (EBER) in situ hybridization, and 34 cases (9.0%) were identified as EBER-positive. EBER positivity was significantly associated with age greater than 60 years (P = .005), more advanced stage (P < .001), more than one extranodal involvement (P = .009), higher International Prognostic Index (IPI) risk group (P = .015), presence of B symptom (P = .004), and poorer outcome to initial treatment (P = .006). The EBER(+) patients with DLBCL demonstrated substantially poorer overall survival (EBER(+) vs EBER(-) 35.8 months [95% confidence interval (CI), 0-114.1 months] vs not reached, P = .026) and progression-free survival (EBER(+) vs EBER(-) 12.8 months [95% CI, 0-31.8 months] vs 35.8 months [95% CI, 0-114.1 months], respectively (P = .018). In nongerminal center B-cell-like subtype, EBER in situ hybridization positivity retained its statistical significance at the multivariate level (P = .045). Nongerminal center B-cell-like patients with DLBCL with EBER positivity showed substantially poorer overall survival with 2.9-fold (95% CI, 1.1-8.1) risk for death. Taken together, DLBCL patients with EBER in situ hybridization+ pursued more rapidly deteriorating clinical course with poorer treatment response, survival, and progression-free survival.
