A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma

Anamarija M. Perry, Teresa M. Cardesa-Salzmann, Paul N. Meyer, Luis Colomo, Lynette M. Smith, Kai Fu, Timothy C. Greiner, Jan Delabie, Randy D. Gascoyne, Lisa Rimsza, Elaine S. Jaffe, German Ott, Andreas Rosenwald, Rita Braziel, Raymond Tubbs, James R. Cook, Louis M. Staudt, Joseph M. Connors, Laurie H. Sehn, Julie M. VoseArmando Loṕez-Guillermo, Elias Campo, Wing C. Chan, Dennis D. Weisenburger

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) <5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.

Original languageEnglish (US)
Pages (from-to)2290-2296
Number of pages7
JournalBlood
Volume120
Issue number11
DOIs
StatePublished - Sep 13 2012

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Biological Models
Lymphoma, Large B-Cell, Diffuse
Immunohistochemistry
Cells
Survival
Gene Expression Profiling
Gene expression
Biological Factors
Vincristine
Stromal Cells
Prednisone
Paraffin
Doxorubicin
Cyclophosphamide
Disease-Free Survival
Cysteine
Microarrays
B-Lymphocytes
Coloring Agents
Multivariate Analysis

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Perry, A. M., Cardesa-Salzmann, T. M., Meyer, P. N., Colomo, L., Smith, L. M., Fu, K., ... Weisenburger, D. D. (2012). A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma. Blood, 120(11), 2290-2296. https://doi.org/10.1182/blood-2012-05-430389

A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma. / Perry, Anamarija M.; Cardesa-Salzmann, Teresa M.; Meyer, Paul N.; Colomo, Luis; Smith, Lynette M.; Fu, Kai; Greiner, Timothy C.; Delabie, Jan; Gascoyne, Randy D.; Rimsza, Lisa; Jaffe, Elaine S.; Ott, German; Rosenwald, Andreas; Braziel, Rita; Tubbs, Raymond; Cook, James R.; Staudt, Louis M.; Connors, Joseph M.; Sehn, Laurie H.; Vose, Julie M.; Loṕez-Guillermo, Armando; Campo, Elias; Chan, Wing C.; Weisenburger, Dennis D.

In: Blood, Vol. 120, No. 11, 13.09.2012, p. 2290-2296.

Research output: Contribution to journalArticle

Perry, AM, Cardesa-Salzmann, TM, Meyer, PN, Colomo, L, Smith, LM, Fu, K, Greiner, TC, Delabie, J, Gascoyne, RD, Rimsza, L, Jaffe, ES, Ott, G, Rosenwald, A, Braziel, R, Tubbs, R, Cook, JR, Staudt, LM, Connors, JM, Sehn, LH, Vose, JM, Loṕez-Guillermo, A, Campo, E, Chan, WC & Weisenburger, DD 2012, 'A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma', Blood, vol. 120, no. 11, pp. 2290-2296. https://doi.org/10.1182/blood-2012-05-430389
Perry, Anamarija M. ; Cardesa-Salzmann, Teresa M. ; Meyer, Paul N. ; Colomo, Luis ; Smith, Lynette M. ; Fu, Kai ; Greiner, Timothy C. ; Delabie, Jan ; Gascoyne, Randy D. ; Rimsza, Lisa ; Jaffe, Elaine S. ; Ott, German ; Rosenwald, Andreas ; Braziel, Rita ; Tubbs, Raymond ; Cook, James R. ; Staudt, Louis M. ; Connors, Joseph M. ; Sehn, Laurie H. ; Vose, Julie M. ; Loṕez-Guillermo, Armando ; Campo, Elias ; Chan, Wing C. ; Weisenburger, Dennis D. / A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma. In: Blood. 2012 ; Vol. 120, No. 11. pp. 2290-2296.
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T1 - A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma

AU - Perry, Anamarija M.

AU - Cardesa-Salzmann, Teresa M.

AU - Meyer, Paul N.

AU - Colomo, Luis

AU - Smith, Lynette M.

AU - Fu, Kai

AU - Greiner, Timothy C.

AU - Delabie, Jan

AU - Gascoyne, Randy D.

AU - Rimsza, Lisa

AU - Jaffe, Elaine S.

AU - Ott, German

AU - Rosenwald, Andreas

AU - Braziel, Rita

AU - Tubbs, Raymond

AU - Cook, James R.

AU - Staudt, Louis M.

AU - Connors, Joseph M.

AU - Sehn, Laurie H.

AU - Vose, Julie M.

AU - Loṕez-Guillermo, Armando

AU - Campo, Elias

AU - Chan, Wing C.

AU - Weisenburger, Dennis D.

PY - 2012/9/13

Y1 - 2012/9/13

N2 - Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) <5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.

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