A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy

William W L Choi, Dennis D. Weisenburger, Timothy C. Greiner, Miguel A. Piris, Alison H. Banham, Jan Delabie, Rita Braziel, Huimin Geng, Javeed Iqbal, Georg Lenz, Julie M. Vose, Christine P. Hans, Kai Fu, Lynette M. Smith, Min Li, Zhongfeng Liu, Randy D. Gascoyne, Andreas Rosenwald, German Ott, Lisa M. RimszaElias Campo, Elaine S. Jaffe, David L. Jaye, Louis M. Staudt, Wing C. Chan

Research output: Contribution to journalArticle

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Abstract

Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with ∼80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm. Experimental Design: Westudied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)-treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2,MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treatedwith rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm. Results: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87%) versus ABC (44%); P <0.001], simulating the predictive power of the GEP classification. For a group of seven primary mediastinal large B-cell lymphoma, the new algorithm is a better prognostic classifier (all "GCB") than the Hans' algorithm (two GCB, five non-GCB). Conclusion: Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials.

Original languageEnglish (US)
Pages (from-to)5494-5502
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number17
DOIs
StatePublished - Sep 1 2009

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Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Germinal Center
Gene Expression Profiling
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Cyclin D2
Observer Variation
B-Cell Lymphoma
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Choi, W. W. L., Weisenburger, D. D., Greiner, T. C., Piris, M. A., Banham, A. H., Delabie, J., ... Chan, W. C. (2009). A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clinical Cancer Research, 15(17), 5494-5502. https://doi.org/10.1158/1078-0432.CCR-09-0113

A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. / Choi, William W L; Weisenburger, Dennis D.; Greiner, Timothy C.; Piris, Miguel A.; Banham, Alison H.; Delabie, Jan; Braziel, Rita; Geng, Huimin; Iqbal, Javeed; Lenz, Georg; Vose, Julie M.; Hans, Christine P.; Fu, Kai; Smith, Lynette M.; Li, Min; Liu, Zhongfeng; Gascoyne, Randy D.; Rosenwald, Andreas; Ott, German; Rimsza, Lisa M.; Campo, Elias; Jaffe, Elaine S.; Jaye, David L.; Staudt, Louis M.; Chan, Wing C.

In: Clinical Cancer Research, Vol. 15, No. 17, 01.09.2009, p. 5494-5502.

Research output: Contribution to journalArticle

Choi, WWL, Weisenburger, DD, Greiner, TC, Piris, MA, Banham, AH, Delabie, J, Braziel, R, Geng, H, Iqbal, J, Lenz, G, Vose, JM, Hans, CP, Fu, K, Smith, LM, Li, M, Liu, Z, Gascoyne, RD, Rosenwald, A, Ott, G, Rimsza, LM, Campo, E, Jaffe, ES, Jaye, DL, Staudt, LM & Chan, WC 2009, 'A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy', Clinical Cancer Research, vol. 15, no. 17, pp. 5494-5502. https://doi.org/10.1158/1078-0432.CCR-09-0113
Choi, William W L ; Weisenburger, Dennis D. ; Greiner, Timothy C. ; Piris, Miguel A. ; Banham, Alison H. ; Delabie, Jan ; Braziel, Rita ; Geng, Huimin ; Iqbal, Javeed ; Lenz, Georg ; Vose, Julie M. ; Hans, Christine P. ; Fu, Kai ; Smith, Lynette M. ; Li, Min ; Liu, Zhongfeng ; Gascoyne, Randy D. ; Rosenwald, Andreas ; Ott, German ; Rimsza, Lisa M. ; Campo, Elias ; Jaffe, Elaine S. ; Jaye, David L. ; Staudt, Louis M. ; Chan, Wing C. / A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 17. pp. 5494-5502.
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abstract = "Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with ∼80{\%} concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm. Experimental Design: Westudied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)-treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2,MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treatedwith rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm. Results: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93{\%} concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87{\%}) versus ABC (44{\%}); P <0.001], simulating the predictive power of the GEP classification. For a group of seven primary mediastinal large B-cell lymphoma, the new algorithm is a better prognostic classifier (all {"}GCB{"}) than the Hans' algorithm (two GCB, five non-GCB). Conclusion: Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials.",
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T1 - A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy

AU - Choi, William W L

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy C.

AU - Piris, Miguel A.

AU - Banham, Alison H.

AU - Delabie, Jan

AU - Braziel, Rita

AU - Geng, Huimin

AU - Iqbal, Javeed

AU - Lenz, Georg

AU - Vose, Julie M.

AU - Hans, Christine P.

AU - Fu, Kai

AU - Smith, Lynette M.

AU - Li, Min

AU - Liu, Zhongfeng

AU - Gascoyne, Randy D.

AU - Rosenwald, Andreas

AU - Ott, German

AU - Rimsza, Lisa M.

AU - Campo, Elias

AU - Jaffe, Elaine S.

AU - Jaye, David L.

AU - Staudt, Louis M.

AU - Chan, Wing C.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with ∼80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm. Experimental Design: Westudied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)-treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2,MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treatedwith rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm. Results: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87%) versus ABC (44%); P <0.001], simulating the predictive power of the GEP classification. For a group of seven primary mediastinal large B-cell lymphoma, the new algorithm is a better prognostic classifier (all "GCB") than the Hans' algorithm (two GCB, five non-GCB). Conclusion: Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials.

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