Abstract 4490: Molecular characteristics of diffuse large B-cell lymphoma in HIV-positive and HIV-negative patients

Abstract

Abstract Introduction: HIV-infected patients are at elevated risk of non-Hodgkin lymphoma (NHL), especially diffuse large B-cell lymphoma (DLBCL), compared with the general population. Because DLBCL is a molecularly and clinically heterogeneous disease, we compared frequencies and prognostic significance of molecular characteristics in HIV+ and HIV- DLBCLs. Methods: Archived formalin-fixed paraffin-embedded tissue specimens from 175 patients with primary DLBCL diagnosed during 1977-2003 were obtained from the Los Angeles County SEER Residual Tissue Repository. Immunohistochemistry was used to evaluate expression of key markers of B-cell differentiation, and fluorescence in situ hybridization was used to detect common NHL-associated translocations involving BCL2, BCL6, and c-Myc [t(14;18)(q32;q21), (t(3;14)(q27;q32), and t(8;14)(q24;q32), respectively]. DLBCLs were distinguished by cell of origin into germinal center B-cell (GCB)-DLBCL and activated B-cell (ABC)-DLBCL according to expression of CD10, GCET1, MUM1, FoxP1, and LMO2 based on the Tally algorithm (Meyer et al., J Clin Oncol 2011). Multivariate Cox regression compared survival according to HIV, cell of origin, and translocation status, adjusting for race/ethnicity, sex, socioeconomic status, age, Los Angeles residence, and initial course of treatment (immunochemotherapy and/or radiotherapy). Results: We identified 54 HIV+ and 121 HIV- patients with DLBCL. All HIV+ patients were male with a median age at diagnosis of 37 years (range 25-58 years) and median year of diagnosis of 1992 (range 1987-1998), whereas HIV- patients were evenly divided by sex with a median age at diagnosis of 65 years (range 16-90 years) and median year of diagnosis of 1992 (range 1977-2003). Among HIV-patients, 104 (86%) were deceased whereas all 54 HIV+ patients were deceased. HIV+ patients had worse prognosis compared to HIV- patients (hazard ratio (HR)=7.55, 95% confidence interval (CI) 4.34-13.12). Compared with patients with HIV-DLBCL, HIV+ patients were more likely to have ABC-DLBCL (HIV-: 46%, HIV+: 71%, p=0.0053), and less likely to have translocations of BCL2 (HIV-: 24%, HIV+: 0%, p<0.0001) and BCL6 (HIV-: 18%, HIV+: 5%, p=0.076). Among both HIV+ and HIV- patients, ABC-DLBCL was associated with adverse prognosis compared with GCB-DLBCL (HIV-: ABC HR=1.76, 95% CI 1.10-2.82, HIV+: ABC HR=2.00, 95% CI 0.93-4.33). In contrast, the presence of BCL2 and BCL6 translocations was associated with adverse prognosis in HIV- patients only (BCL2 HR=1.79, 95% CI 1.09-2.93, BCL6 HR=2.07, 95% CI 1.08-3.64). Conclusions: HIV+ and HIV- DLBCLs differ significantly with respect to key molecular characteristics, supporting biologic differences in the lymphomagenic process in the presence of HIV. The well-recognized adverse prognosis among HIV+ patients with DLBCL may be due in part to the higher proportion of ABC-DLBCLs compared to HIV- patients with DLBCL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4490. doi:1538-7445.AM2012-4490