Originally published as JCO Early Release 10.1200/JCO.2007.13.0690 on December 17 2007

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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.

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