title: 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 (pHIV-infected = 0.066; pHIV-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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS , Rockville, MD , USA.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.forename: Clara J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Kishor
authors.initials: K
authors.lastname: Bhatia
authors.forename: Myles
authors.initials: M
authors.lastname: Cockburn
authors.forename: Debra
authors.initials: D
authors.lastname: Hawes
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Cindy
authors.initials: C
authors.lastname: Chang
authors.forename: Sean F
authors.initials: SF
authors.lastname: Altekruse
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023241:Antiretroviral Therapy, Highly Active; D014408:Biomarkers, Tumor / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor