Clinical impact of serum survivin positivity and tissue expression of EBV-encoded RNA in diffuse large B-cell lymphoma patients treated with rituximab-CHOPopen access
- Authors
- Hong, Jung Yong; Ryu, Kyung Ju; Park, Chaehwa; Hong, Mineui; Ko, Young Hyeh; Kim, Won Seog; Kim, Seok Jin
- Issue Date
- Feb-2017
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- survivin; epstein-barr virus; diffuse large B-cell lymphoma
- Citation
- ONCOTARGET, v.8, no.8, pp 13782 - 13791
- Pages
- 10
- Journal Title
- ONCOTARGET
- Volume
- 8
- Number
- 8
- Start Page
- 13782
- End Page
- 13791
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69721
- DOI
- 10.18632/oncotarget.14636
- ISSN
- 1949-2553
1949-2553
- Abstract
- Survivin is an inhibitor of apoptosis and is upregulated by Epstein-Barr virus (EBV) latent genes. Given the frequent association of EBV with lymphoid malignancies, survivin is expected to have prognostic value in diffuse large B-cell lymphoma (DLBCL). Thus, we measured the pretreatment serum level of survivin in DLBCL patients and analyzed its association with survival outcome and EBV status, as represented by EBV-encoded RNA (EBER) in DLBCL. Pretreatment serum survivin level was measured in patients registered in a prospective cohort study (n = 210), and serum survivin-positivity was defined as any detectable level of survivin. EBV status was determined using EBER in situ hybridization, and EBER-positivity was defined as 20% of examined cells showing nuclear positivity. Mean serum survivin level was higher in patients with relapsed or refractory disease than with responsive disease (59.89 pg/mL versus 17.34 pg/mL, P = 0.041). Serum survivin-positive patients had worse overall and progression- free survival (P = 0.023 and 0.022, respectively). Serum survivin positivity was associated with unfavorable characteristics including stage. In patients with non-germinal center B-cell type DLBCL, serum survivin-positive patients also had significantly worse survival than serum survivin-negative patients (P < 0.001). EBER-positivity was found in 6.7% (14/210) of patients, and EBER-positive patients had worse survival (P < 0.05). Patients having concomitant positivity for serum survivin and EBER expression (2.8%, 6/210) showed extremely poor prognosis. In the present era of rituximab in DLBCL, DLBCL with serum survivin positivity showed adverse clinical features and followed worse clinical course, especially in non-GCB subtype DLBCL. EBER-positivity was still associated with worse outcomes in DLBCL.
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