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 language | English (US) |
|---|---|
| Pages (from-to) | 3425-3433 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 112 |
| Issue number | 8 |
| DOIs | |
| State | Published - Oct 15 2008 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP
AU - Rimsza, Lisa M.
AU - LeBlanc, Michael L.
AU - Unger, Joseph M.
AU - Miller, Thomas P.
AU - Grogan, Thomas M.
AU - Persky, Daniel O.
AU - Mattel, Ralph R.
AU - Sabalos, Constantine M.
AU - Seligmann, Bruce
AU - Braziel, Rita
AU - Campo, Elias
AU - Rosenwald, Andreas
AU - Connors, Joseph M.
AU - Sehn, Laurie H.
AU - Johnson, Nathalie
AU - Gascoyne, Randy D.
PY - 2008/10/15
Y1 - 2008/10/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2008-02-137372
DO - 10.1182/blood-2008-02-137372
M3 - Article
VL - 112
SP - 3425
EP - 3433
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -