Originally published as JCO Early Release 10.1200/JCO.2007.13.0690 on December 17 2007
Journal of Clinical Oncology, Vol 26, No 3 (January 20), 2008: pp. 447-454
© 2008 American Society of Clinical Oncology.
LMO2 Protein Expression Predicts Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With Anthracycline-Based Chemotherapy With and Without Rituximab
Yasodha Natkunam,
Pedro Farinha,
Eric D. Hsi,
Christine P. Hans,
Robert Tibshirani,
Laurie H. Sehn,
Joseph M. Connors,
Dita Gratzinger,
Manuel Rosado,
Shuchun Zhao,
Brad Pohlman,
Nicholas Wongchaowart,
Martin Bast,
Abraham Avigdor,
Ginette Schiby,
Arnon Nagler,
Gerald E. Byrne,
Ronald Levy,
Randy D. Gascoyne,
Izidore S. Lossos
From the Department of Pathology and Department of Medicine, Division of Oncology, Stanford University School of Medicine; Departments of Health Research and Policy and Statistics, Stanford University, Stanford, CA; Departments of Clinical Pathology and Hematologic Oncology and Blood Disorders, Cleveland Clinic Foundation, Cleveland, OH; Departments of Pathology and Medicine, University of Nebraska Medical Center, Omaha, NE; Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, and Department of Pathology, University of Miami, Miami, FL; Department of Pathology and Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; and Chaim-Sheba Medical Center, Tel-Aviv, Israel
Corresponding author: Izidore S. Lossos, MD, Sylvester Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of Miami, 1475NW 12th Ave (D8-4), Miami, FL 33136; e-mail: ilossos{at}med.miami.edu
Purpose The heterogeneity of diffuse large B-cell lymphoma (DLBCL) has prompted the search for new markers that can accurately separate prognostic risk groups. We previously showed in a multivariate model that LMO2 mRNA was a strong predictor of superior outcome in DLBCL patients. Here, we tested the prognostic impact of LMO2 protein expression in DLBCL patients treated with anthracycline-based chemotherapy with or without rituximab.
Patients and Methods DLBCL patients treated with anthracycline-based chemotherapy alone (263 patients) or with the addition of rituximab (80 patients) were studied using immunohistochemistry for LMO2 on tissue microarrays of original biopsies. Staining results were correlated with outcome.
Results In anthracycline-treated patients, LMO2 protein expression was significantly correlated with improved overall survival (OS) and progression-free survival (PFS) in univariate analyses (OS, P = .018; PFS, P = .010) and was a significant predictor independent of the clinical International Prognostic Index (IPI) in multivariate analysis. Similarly, in patients treated with the combination of anthracycline-containing regimens and rituximab, LMO2 protein expression was also significantly correlated with improved OS and PFS (OS, P = .005; PFS, P = .009) and was a significant predictor independent of the IPI in multivariate analysis.
Conclusion We conclude that LMO2 protein expression is a prognostic marker in DLBCL patients treated with anthracycline-based regimens alone or in combination with rituximab. After further validation, immunohistologic analysis of LMO2 protein expression may become a practical assay for newly diagnosed DLBCL patients to optimize their clinical management.
published online ahead of print at www.jco.org on December 17, 2007.
Supported by Grant Nos. NIH CA109335, NIH CA34233, NIH CA 33399, and CA122105 from the National Institutes of Health, a Leukemia and Lymphoma Society SCORE grant, National Cancer Institute of Canada Terry Fox Program Project Grant No. 016003, Grant No. 06BCBG113 from the Bankhead-Coley Foundation, FL, and the Dwoskin Family Foundation.
R.D.G. and I.S.L. contributed equally to this work.
Authors disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike Complore Connotea Del.icio.us Digg Facebook Reddit Technorati Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
C. Copie-Bergman, P. Gaulard, K. Leroy, J. Briere, M. Baia, J.-P. Jais, G. A. Salles, F. Berger, C. Haioun, H. Tilly, et al.
Immuno-Fluorescence In Situ Hybridization Index Predicts Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP: A GELA Study
J. Clin. Oncol.,
November 20, 2009;
27(33):
5573 - 5579.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. W.L. Choi, D. D. Weisenburger, T. C. Greiner, M. A. Piris, A. H. Banham, J. Delabie, R. M. Braziel, H. Geng, J. Iqbal, G. Lenz, et al.
A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy
Clin. Cancer Res.,
September 1, 2009;
15(17):
5494 - 5502.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Appert, C.-H. Nam, N. Lobato, E. Priego, R. N. Miguel, T. Blundell, L. Drynan, H. Sewell, T. Tanaka, and T. Rabbitts
Targeting LMO2 with a Peptide Aptamer Establishes a Necessary Function in Overt T-Cell Neoplasia
Cancer Res.,
June 1, 2009;
69(11):
4784 - 4790.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Malumbres, K. A. Sarosiek, E. Cubedo, J. W. Ruiz, X. Jiang, R. D. Gascoyne, R. Tibshirani, and I. S. Lossos
Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas
Blood,
April 16, 2009;
113(16):
3754 - 3764.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Gratzinger, S. Zhao, R. West, R. V. Rouse, H. Vogel, E. C. Gil, R. Levy, I. S. Lossos, and Y. Natkunam
The Transcription Factor LMO2 Is a Robust Marker of Vascular Endothelium and Vascular Neoplasms and Selected Other Entities
Am J Clin Pathol,
February 1, 2009;
131(2):
264 - 278.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Eng
Microenvironmental Protection in Diffuse Large-B-Cell Lymphoma
N. Engl. J. Med.,
November 27, 2008;
359(22):
2379 - 2381.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. D. Brooks, R. M. Graham, R. L. Woodford, A. K. Bennett, X. Q. Wang, M. E. Williams, and J. B. Cousar
LMO2 and Bcl-6 Expression in Diffuse Large B-Cell Lymphoma Predict Overall Survival in R-CHOP Treated Patients
Blood (ASH Annual Meeting Abstracts),
November 16, 2008;
112(11):
5304 - 5304.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
X. Lu, R. Malumbres, B. Shields, X. Jiang, K. A. Sarosiek, Y. Natkunam, T. Tiganis, and I. S. Lossos
PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling
Blood,
November 15, 2008;
112(10):
4098 - 4108.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. M. Rimsza, M. L. LeBlanc, J. M. Unger, T. P. Miller, T. M. Grogan, D. O. Persky, R. R. Martel, C. M. Sabalos, B. Seligmann, R. M. Braziel, et al.
Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP
Blood,
October 15, 2008;
112(8):
3425 - 3433.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Malumbres, J. Chen, R. Tibshirani, N. A. Johnson, L. H. Sehn, Y. Natkunam, J. Briones, R. Advani, J. M. Connors, G. E. Byrne, et al.
Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP
Blood,
June 15, 2008;
111(12):
5509 - 5514.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|