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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4251-4258.
Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-07-2365.
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NEOPLASIA
Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project
Lisa M. Rimsza,
Robin A. Roberts,
Thomas P. Miller,
Joseph M. Unger,
Michael LeBlanc,
Rita M. Braziel,
Dennis D. Weisenberger,
Wing C. Chan,
H. Konrad Muller-Hermelink,
Elaine S. Jaffe,
Randy D. Gascoyne,
Elias Campo,
Deborah A. Fuchs,
Catherine M. Spier,
Richard I. Fisher,
Jan Delabie,
Andreas Rosenwald,
Louis M. Staudt, and
Thomas M. Grogan
From the Departments of Pathology and Internal Medicine, University of Arizona, Tucson, AZ; Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Pathology, Oregon Health Sciences Center, Portland, OR; Department of Pathology, University of Nebraska, Omaha, NE; Department of Pathology, University of Wuerzburg, Wuerzburg, Germany; Metabolism Branch, National Cancer Institute, Bethesda, MD; British Columbia Cancer Agency, Vancouver, BC, Canada; Hospital Clinic Provincial, University of Barcelona, Barcelona, Spain; James P. Wilmot Cancer Center, University of Rochester, Rochester, NY; and the Norwegian Radium Hospital, Oslo, Norway.
The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better survival. We further analyzed the effects of HLA-DRA on survival and correlated gene expression with protein status and tumor-infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10% of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group, and 55% for patients in the highest 50%. Further analysis demonstrated that the hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment for the International Prognostic Index did not alter the impact of HLA-DRA on survival. Other MHC class II genes were found to predict survival similarly. Microarray HLA-DRA expression correlated with the presence or absence of human leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor-infiltrating CD8+ T cells were detected in MHC class II-negative cases compared with positive cases (2.8% versus 11.0%; P = .001), supporting the hypothesis that loss of tumor immunosurveillance has a devastating effect on patient outcome in DLBCL. (Blood. 2004; 103:4251-4258)
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