Gene Expression Predicts Overall Survival in Paraffin-embedded Tissues of Diffuse Large B-cell Lymphoma Treated with R-CHOP

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2008 Jun 12

PMID 18544678

Citations 73

Authors

Lisa M Rimsza

Michael L LeBlanc

Joseph M Unger

Thomas P Miller

Thomas M Grogan

Daniel O Persky

Ralph R Martel

Constantine M Sabalos

Bruce Seligmann

Rita M Braziel

Elias Campo

Andreas Rosenwald

Joseph M Connors

Laurie H Sehn

Nathalie Johnson

Randy D Gascoyne

Affiliations

Soon will be listed here.

Abstract

Gene expression profiling (GEP) on frozen tissues has identified genes predicting outcome in patients with diffuse large B-cell lymphoma (DLBCL). Confirmation of results in current patients is limited by availability of frozen samples and addition of monoclonal antibodies to treatment regimens. We used a quantitative nuclease protection assay (qNPA) to analyze formalin-fixed, paraffin-embedded tissue blocks for 36 previously identified genes (N = 209, 93 chemotherapy; 116 rituximab + chemotherapy). By qNPA, 208 cases were successfully analyzed (99.5%). In addition, 15 of 36 and 11 of 36 genes, representing each functional group previously identified by GEP, were associated with survival (P < .05) in the 2 treatment groups, respectively. In addition, 30 of 36 hazard ratios of death trended in the same direction versus the original studies. Multivariate and variable cut-off point analysis identified low levels of HLA-DRB (< 20%) and high levels of MYC (> 80%) as independent indicators of survival, together distinguishing cases with the worst prognosis. Our results solve a clinical research problem by demonstrating that prognostic genes can be meaningfully quantified using qNPA technology on formalin-fixed, paraffin-embedded tissues; previous GEP findings in DLBCL are relevant with current treatments; and 2 genes, representing immune escape and proliferation, are the common features of the most aggressive DLBCL.

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