title: A comparative study of molecular characteristics of diffuse large B-cell lymphoma from patients with and without human immunodeficiency virus infection.
abstract: OBJECTIVE
  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 significance of selected oncogenic markers in DLBCL diagnosed at Kaiser Permanente in California, between 1996 and 2007.
  
  
  METHODS
  Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender, and race. Twenty-three markers 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. For markers differentially expressed in HIV-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-of-origin phenotype, and DLBCL morphologic variants.
  
  
  RESULTS
  Expression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-β2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was significantly elevated in HIV-related DLBCLs, whereas expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased 2-year mortality in HIV-infected patients [relative risk = 3.09 (0.90-10.55)] in multivariable logistic regression.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California. chun.r.chao@kp.org.
authors.forename: Chun
authors.initials: C
authors.lastname: Chao
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Silverberg
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Lie-Hong
authors.initials: LH
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California.
authors.forename: Brandon
authors.initials: B
authors.lastname: Castor
authors.affiliation: Departments of Obstetrics and Gynecology and Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, California. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California.
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
authors.affiliation: Department of Medicine and San Francisco General Hospital, University of California, San Francisco, San Francisco, California.
authors.forename: Donald I
authors.initials: DI
authors.lastname: Abrams
authors.affiliation: Los Angeles Medical Center, Kaiser Permanente Southern California, Los Angeles, California.
authors.forename: Hongbin D
authors.initials: HD
authors.lastname: Zha
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Reina
authors.initials: R
authors.lastname: Haque
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000401:mortality / Q000821:virology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000401:mortality / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D064546:Protein Kinase C beta / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; D007075:Immunoglobulin M; D050835:Interferon Regulatory Factors; D018809:Proliferating Cell Nuclear Antigen; D064546:Protein Kinase C beta; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C497483:CD44 protein, human; C489427:MYC protein, human; C413374:p27 antigen