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Annals of Oncology Advance Access published online on October 29, 2009
Annals of Oncology, doi:10.1093/annonc/mdp460
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Prognostic value of regulatory T cells, lymphoma-associated macrophages, and MUM-1 expression in follicular lymphoma treated before and after the introduction of monoclonal antibody therapy: a Southwest Oncology Group Study

J. W. Sweetenham1,*, B. Goldman2, M. L. LeBlanc2, J. R. Cook3, R. R. Tubbs3, O. W. Press4, D. G. Maloney4, R. I. Fisher5, L. M. Rimsza6, R. M. Braziel7 and E. D. Hsi3

1 Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland
2 Southwest Oncology Group Statistical Center, Seattle
3 Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland
4 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle
5 Department of Medicine, University of Rochester Cancer, Rochester
6 Department of Pathology, University of Arizona, Tucson
7 Department of Pathology, Oregon Health Sciences University, Portland, USA

* Correspondence to: Dr J. W. Sweetenham, Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel: +1-216-445-6707; Fax: +1-216-444-9464; E-mail: sweetej{at}ccf.org

Background: The purpose was to examine the prognostic impact of features of tumor cells and immune microenvironment in patients with follicular lymphoma treated with and without anti-CD20 monoclonal antibody therapy.

Patients and methods: Tissue microarrays were constructed from archived tissue obtained from patients on three sequential Southwest Oncology Group (SWOG) trials for FL. All three trials included anthracycline-based chemotherapy. Anti-CD20 monoclonal antibodies were included for patients in the latter two trials. Immunohistochemistry was used to study the number and distribution of cells staining for forkhead box protein P3 (FOXP3) and lymphoma-associated macrophages (LAMs) and the number of lymphoma cells staining for myeloma-associated antigen-1 (MUM-1). Cox proportional hazards regression was used to evaluate the association between marker expression and overall survival (OS).

Results: The number or pattern of infiltrating FOXP3 cells and LAMs did not correlate with OS in sequential SWOG studies for FL. The presence of MUM-1 correlated with lower OS for patients who received monoclonal antibody but not for those treated with chemotherapy alone.

Conclusions: Immune cell composition of lymph nodes did not correlate with OS in this analysis of trials in FL. The mechanism of the observed correlation between MUM-1 expression and adverse prognosis in patients receiving monoclonal antibody therapy requires confirmation.

follicular lymphoma, LAMs, MUM-1, prognosis, Tregs

Received for publication March 31, 2009. Revision received June 29, 2009. Accepted for publication August 10, 2009.


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