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Epstein-Barr virus infection and expression of B-cell oncogenic markers in HIV-related diffuse large B-cell Lymphoma.

ABSTRACT: Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-?B pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs.

SUBMITTER: Chao C

PROVIDER: S-EPMC3846529 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Epstein-Barr virus infection and expression of B-cell oncogenic markers in HIV-related diffuse large B-cell Lymphoma.

Chao Chun C Silverberg Michael J MJ Martínez-Maza Otoniel O Chi Margaret M Abrams Donald I DI Haque Reina R Zha Hongbin D HD McGuire Michelle M Xu Lanfang L Said Jonathan J

Clinical cancer research : an official journal of the American Association for Cancer Research 20120618 17

<h4>Purpose</h4>Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.<h4>Experimental design</h4>HIV-related DLBCL cases diagnosed between 1996 and 2007 withi ...[more]

PMID: 22711707

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Project description:Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is subdivided according to the cell-of-origin (COO) classification into germinal centre B-cell (GCB) and activated B-cell (ABC) subtypes, each with different molecular profiles and clinical behaviour. This study aims to describe the pattern of the COO subtypes, the proportion of Epstein-Barr virus (EBV) co-infection, and their influence on survival outcomes in a setting of high HIV prevalence. This retrospective cohort study included patients diagnosed with de novo DLBCL NOS at our tertiary academic centre in Cape Town, South Africa over a 14-year period. Immunohistochemical stains were performed for COO classification, according to the Hans algorithm. Tumour EBV co-infection was established by EBV-encoded ribonucleic acid in situ hybridisation (EBER-ISH) staining. The effect of the COO subtypes and EBV co-infection on overall survival were described by means of univariate, bivariate and multivariate analyses. A total of 181 patients with DLBCL NOS were included, which comprised 131 HIV-uninfected and 50 HIV-infected patients. There was an equal distribution of GCB and ABC subtypes in the HIV-infected and HIV-uninfected groups. EBV co-infection was detected in 16% of the HIV-infected cases and in 7% of the HIV-uninfected cases (p=0.09). There was no significant difference in the incidence of EBV co-infection between the GCB and ABC subtypes (p=0.67). HIV-infected patients with CD4 ≥150 cells/mm3 had similar survival to HIV-uninfected patients (p=0.005). Multivariate regression analysis showed that in the HIV-infected group with marked immunosuppression (CD4 <150 cells/mm3), there was significantly poorer overall survival compared to the HIV-uninfected group (HR 2.4, 95% CI 1.3-4.1). There were no statistically significant differences in overall survival by DLBCL COO subtype. There was no difference in the proportion of DLBCL COO subtypes, regardless of HIV status. EBV co-infection was more common in the HIV-infected group, but less than described in the literature. Unexpectedly, there were no significant differences in survival outcomes between the GCB and ABC subtypes. Higher CD4 counts in the HIV-infected group had good survival outcomes, while lower CD4 counts predicted adverse survival outcomes. Further research is needed to explore the genetic mutational landscape of HIV-associated DLBCL.

Dataset Information

Epstein-Barr virus infection and expression of B-cell oncogenic markers in HIV-related diffuse large B-cell Lymphoma.

Publications

Epstein-Barr virus infection and expression of B-cell oncogenic markers in HIV-related diffuse large B-cell Lymphoma.

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