Abstract 5353: Identification of a subset of AIDS related lymphoma (ARL) containing HIV infected macrophages that is immunophenotypically distinct from EBV+ ARL

Abstract

Abstract The risk of developing non-Hodgkin lymphoma is 60X greater in the HIV-infected population when compared to non-infected individuals despite the initiation of highly active antiretroviral therapy (HAART). The primary difference between lymphoma in non-infected individuals and those with AIDS related lymphoma (ARL) is that ARL is high-grade and metastatic. Since the introduction of HAART the incidence of ARL has decreased but not the same extent as other AIDS-related malignancies and there has been little change amongst the CD4 strata. Therefore, with the increase in life expectancy afforded by HAART, the overall number of ARL cases is expected to rise in the future. Preliminary reports have suggested that some ARLs contain HIV-infected macrophages that may contribute to ARL pathogenesis. A recent study evaluating HIV sequence evolution in the contest of metastatic ARL found lymphoma specific HIV compartmentalized within sites of lymphoma that was distinct from HIV present in non-lymphoma sites (Salemi et al, PLOSone Dec 3, 2009). These data suggested the existence of a lymphoma specific form of HIV evolving within individuals who develop ARL. The goal of this research was to determine the incidence of HIV infected lymphomas in the pre and post-HAART eras and if HIV-positive lymphomas have a specific immunophenotype. A tissue microarray containing ∼150 of ARLs (from 1982-2007) was obtained through the AIDS and Cancer Specimen Resource (ACSR) and was used for HIV p24 and macrophage CD68 immunohistochemistry. Double staining techniques confirmed that p24 expression was localized to tumor associated macrophages (TAM). There was a highly significant (p<0.001) increase in the frequency of p24+ ARL cases post-HAART (after 1996; 49%) as compared to pre-HAART (before 1996; 26%). Using antigen expression data CD20, CD3, CD10, BCL6, BCL2, MUM1, Ki67, blimp, p53 and EBV, provided by the ACSR, we were able to determine that p24+ ARLs were generally of B cell origin but did not have a specific immunophenotype. In contrast, EBV+ ARLs were more likely to express MUM1 or blimp and less likely to express CD29, CD10 or BCL6. EBV status was not associated with a pre/post HAART diagnosis (44 vs. 40%). However, a subset of EBV-/p24+ tumors was identified. In the pre-HAART era, 13% of the tumors were EBV-/p24+ compared to 30% in the post-HAART era suggesting, that the incidence of this tumor type is increasing (p<0.05). These data describe for the first time the existence of potentially tumor specific HIV in up to 1/3 of all post HAART ARLs, a class of tumor that is immunophenotypically distinct from EBV+ ARLs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5353.