|
|
Blood, 15 October 2008, Vol. 112, No. 8, pp. 3425-3433.
Prepublished online as a Blood First Edition Paper on June 10, 2008; DOI 10.1182/blood-2008-02-137372.
 Previous Article | Next Article 
Submitted February 5, 2008
Accepted May 17, 2008
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 Martel, Constantine M Sabalos, Bruce Seligmann, Rita M Braziel, Elias Campo, Andreas Rosenwald, Joseph M Connors, Laurie H Sehn, Nathalie Johnson, and Randy D Gascoyne
Pathology Department, University of Arizona, Tucson, AZ, United States
Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, WA, United States
Arizona Cancer Center, University of Arizona, Tucson, AZ, United States
High Throughput Genomics, Inc., Tucson, AZ, United States
Pathology Department, OHSU, Portland, OR, United States
Pathology Department, University of Barcelona, Barcelona, Spain
Pathology Department, Universtiy of Wurzberg, Wurzburg, Germany
Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
Pathology Department, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
* Corresponding author; email: lrimsza{at}email.arizona.edu.
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 (FFPET) blocks for 36 previously identified genes (N=209, 93 chemotherapy; 116 rituximab+chemotherapy). By qNPA, 208 cases were successfully analyzed (99.5%). Additionally, 15/36 and 11/36 genes, representing each functional group previously identified by GEP, were associated with survival (p < 0.05) in the 2 treatment groups respectively. Additionally, 30/36 hazard ratios of death trended in the same direction compared to the original studies. Multivariate and variable cut point analysis identified low levels of HLA-DR (<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 the qNPA technology on FFPET blocks; 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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Blocks to paraffin get the CHOP, +R
- Richard Byers
Blood 2008 112: 3006-3007.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
H.-W. Bernd, M. Ziepert, C. Thorns, W. Klapper, H.-H. Wacker, M. Hummel, H. Stein, M.-L. Hansmann, G. Ott, A. Rosenwald, et al.
Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials
Haematologica,
November 1, 2009;
94(11):
1569 - 1580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Vitolo, A. Chiappella, E. Angelucci, G. Rossi, A. M. Liberati, M. G. Cabras, B. Botto, G. Ciccone, G. Gaidano, L. Falchi, et al.
Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study
Haematologica,
September 1, 2009;
94(9):
1250 - 1258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Rimsza, W. C. Chan, R. D. Gascoyne, E. Campo, E. S. Jaffe, L. M. Staudt, J. Delabie, A. Rosenwald, and S. P. Murphy
CIITA or RFX coding region loss of function mutations occur rarely in diffuse large B-cell lymphoma cases and cell lines with low levels of major histocompatibility complex class II expression
Haematologica,
April 1, 2009;
94(4):
596 - 598.
[Full Text]
[PDF]
|
|
|
|
|
