Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP

Lisa M. Rimsza, Michael L. LeBlanc, Joseph M. Unger, Thomas P. Miller, Thomas M. Grogan, Daniel O. Persky, Ralph R. Mattel, Constantine M. Sabalos, Bruce Seligmann, Rita Braziel, Elias Campo, Andreas Rosenwald, Joseph M. Connors, Laurie H. Sehn, Nathalie Johnson, Randy D. Gascoyne

Research output: Contribution to journalArticle

108 Citations (Scopus)

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; 116rituximab + 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, paraffinembedded 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.

Original languageEnglish (US)
Pages (from-to)3425-3433
Number of pages9
JournalBlood
Volume112
Issue number8
DOIs
StatePublished - Oct 15 2008

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Lymphoma, Large B-Cell, Diffuse
Gene expression
Nuclease Protection Assays
Paraffin
Genes
Cells
Tissue
Gene Expression
Gene Expression Profiling
Survival
Assays
Chemotherapy
Formaldehyde
Drug Therapy
Functional groups
Monoclonal Antibodies
Availability
Technology
Therapeutics
Research

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Rimsza, L. M., LeBlanc, M. L., Unger, J. M., Miller, T. P., Grogan, T. M., Persky, D. O., ... Gascoyne, R. D. (2008). Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP. Blood, 112(8), 3425-3433. https://doi.org/10.1182/blood-2008-02-137372

Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP. / Rimsza, Lisa M.; LeBlanc, Michael L.; Unger, Joseph M.; Miller, Thomas P.; Grogan, Thomas M.; Persky, Daniel O.; Mattel, Ralph R.; Sabalos, Constantine M.; Seligmann, Bruce; Braziel, Rita; Campo, Elias; Rosenwald, Andreas; Connors, Joseph M.; Sehn, Laurie H.; Johnson, Nathalie; Gascoyne, Randy D.

In: Blood, Vol. 112, No. 8, 15.10.2008, p. 3425-3433.

Research output: Contribution to journalArticle

Rimsza, LM, LeBlanc, ML, Unger, JM, Miller, TP, Grogan, TM, Persky, DO, Mattel, RR, Sabalos, CM, Seligmann, B, Braziel, R, Campo, E, Rosenwald, A, Connors, JM, Sehn, LH, Johnson, N & Gascoyne, RD 2008, 'Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP', Blood, vol. 112, no. 8, pp. 3425-3433. https://doi.org/10.1182/blood-2008-02-137372
Rimsza, Lisa M. ; LeBlanc, Michael L. ; Unger, Joseph M. ; Miller, Thomas P. ; Grogan, Thomas M. ; Persky, Daniel O. ; Mattel, Ralph R. ; Sabalos, Constantine M. ; Seligmann, Bruce ; Braziel, Rita ; Campo, Elias ; Rosenwald, Andreas ; Connors, Joseph M. ; Sehn, Laurie H. ; Johnson, Nathalie ; Gascoyne, Randy D. / Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP. In: Blood. 2008 ; Vol. 112, No. 8. pp. 3425-3433.
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AU - Grogan, Thomas M.

AU - Persky, Daniel O.

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AU - Braziel, Rita

AU - Campo, Elias

AU - Rosenwald, Andreas

AU - Connors, Joseph M.

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