Biology of Human Tumors A Comparative Study of Molecular Characteristics of Diffuse Large B-cell Lymphoma from Patients with and without Human Immunodeficiency Virus Infection

Purpose: HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically different from DLBCL in the general population. We compared, by HIV status, the expression and prognostic significanceof selectedoncogenicmarkers inDLBCLdiagnosed at Kaiser Permanente in California, between 1996 and 2007. Experimental Design: Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender, and race. Twenty-threemarkers in the following categories were examined using IHC: (i) cell-cycle regulators, (ii) B-cell activators, (iii) antiapoptotic proteins, and (iv) others, such as IgM. Tumor marker expression was compared across HIV infection status by Fisher exact test. Formarkers differentially expressed inHIV-related DLBCL, logistic regression was used to evaluate the association between tumor marker expression and 2-year overall mortality, adjusting for International Prognostic Index, cell-oforigin phenotype, and DLBCL morphologic variants. Results: Expression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-b2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was significantly elevated inHIV-related DLBCLs, whereas expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased 2yearmortality inHIV-infected patients [relative risk1⁄4 3.09 (0.90– 10.55)] in multivariable logistic regression. Conclusion: These results suggest that HIV-related DLBCL pathogenesis more frequently involves cMYC and BCL6 among other factors. In particular, cMYC-mediated pathogenesis may partly explain the more aggressive clinical course of DLBCL in HIV-infected patients. Clin Cancer Res; 21(6); 1–9. 2015 AACR.