Molecular characteristics of diffuse large B-cell lymphoma in human immunodeficiency virus-infected and -uninfected patients in the pre-highly active antiretroviral therapy and pre-rituximab era

Abstract

Human immunodeficiency virus (HIV) infection substantially elevates diffuse large B-cell lymphoma (DLBCL) risk, but its impact on the distinct DLBCL subtypes defined by cell of origin is unclear. We compared DLBCL molecular characteristics and prognosis in 51 HIV-infected and 116 HIV-uninfected cases diagnosed during 1977–2003. Using immunohistochemistry to classify cell of origin based on the Tally algorithm, activated B-cell (ABC)-DLBCL was substantially more common in HIV-infected (83%) than in HIV-uninfected (54%) cases (p < 0.001). Epstein–Barr virus (EBV) was detected in 63% of DLBCLs in HIV-infected cases, occurring almost exclusively in ABC-DLBCL (74% vs. 13% of germinal center B-cell [GCB]-DLBCL, p = 0.002), but was rarely detected in DLBCLs among HIV-uninfected cases (3%). Among HIV-uninfected cases, MYC/IgH [t(8;14)(q24;q32)] and IgH/BCL2 [t(14;18)(q32;q21)] translocations were significantly more common and BCL6/IgH [t(3;14)(q27;q32)] significantly less common in GCB-DLBCL than in ABC-DLBCL (p = 0.010, < 0.001 and = 0.039, respectively). Among HIV-infected cases, translocations other than MYC/IgH [t(8;14)(q24;q32)] (21%) were rare (≤ 6%) and unrelated to cell of origin. ABC-DLBCL was associated with adverse overall survival compared with GCB-DLBCL regardless of HIV status (p_HIV-infected = 0.066; p_{HIV-uninfected} = 0.038). Our data demonstrate key differences in the molecular characteristics, cell of origin and prognosis of DLBCL by HIV status in the pre-highly active antiretroviral therapy (HAART) and pre-rituximab era, supporting biologic differences in lymphomagenesis in the presence of HIV.

Keywords::

• Diffuse large B-cell lymphoma
• Epstein–Barr virus
• activated B-cell
• germinal center B-cell

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This study was supported by the Intramural Program of the National Cancer Institute (National Institutes of Health). The NCI contract for the Los Angeles Residual Tissue Repository support was NO1-PC-35139 (Los Angeles). The collection of data used in this publication was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services under Contract No. N01-PC-2010-00035; and grant number 1U58DP000807-3 from the Centers for Disease Control and Prevention.

The paper was presented in part in abstract form at the 19th Conference on Retroviruses and Opportunistic Infections (5–8 March 2012, Seattle, WA) and the 2012 American Association for Cancer Research Annual Meeting (31 March–4 April 2012, Chicago, IL).