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PMID: 18086797 Published · ppublish English Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Natkunam Y, Farinha P, Hsi ED, Hans CP, Tibshirani R, Sehn LH, Connors JM, Gratzinger D, Rosado M, Zhao S, Pohlman B, Wongchaowart N, Bast M, Avigdor A, Schiby G, Nagler A, Byrne GE, Levy R, Gascoyne RD, Lossos IS

Abstract

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. 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. 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. 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.

MeSH Terms
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
Chemicals
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
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Natkunam Yasodha
Department of Pathology, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Farinha Pedro
Hsi Eric D
Hans Christine P
Tibshirani Robert
Sehn Laurie H
Connors Joseph M
Gratzinger Dita
Rosado Manuel
Zhao Shuchun
Pohlman Brad
Wongchaowart Nicholas
Bast Martin
Avigdor Abraham
Schiby Ginette
Nagler Arnon
Byrne Gerald E
Levy Ronald
Gascoyne Randy D
Lossos Izidore S
Article Info
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Abbr.
J Clin Oncol
ISSN
1527-7755
Published
2008-01-20
Epub
2007-00-17
Pages
447-54
Language
English
Region
United States
NLM ID
8309333
Subset
IM
Grants
NCI NIH HHS · CA 33399 · United States
NCI NIH HHS · CA109335 · United States
NCI NIH HHS · CA122105 · United States
NCI NIH HHS · CA34233 · United States
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