LMO2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy with and without rituximab.

Abstract

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 3 Pg. 447-54 (Jan 20 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18086797 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Biomarkers, Tumor
• DNA-Binding Proteins
• LIM Domain Proteins
• LMO2 protein, human
• Metalloproteins
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-6
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adaptor Proteins, Signal Transducing
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor
• Cohort Studies
• Cyclophosphamide (administration & dosage)
• DNA-Binding Proteins (metabolism)
• Doxorubicin (administration & dosage)
• Humans
• Immunoenzyme Techniques
• LIM Domain Proteins
• Lymphoma, Large B-Cell, Diffuse (drug therapy, metabolism, mortality)
• Metalloproteins (metabolism)
• Middle Aged
• Prednisone (administration & dosage)
• Prognosis
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-6 (metabolism)
• Rituximab
• Survival Rate
• Tissue Array Analysis
• Treatment Outcome
• Vincristine (administration & dosage)