Originally published as JCO Early Release 10.1200/JCO.2008.20.5450 on September 14 2009

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Immunophenotypic Analysis of AIDS-Related Diffuse Large B-Cell Lymphoma and Clinical Implications in Patients From AIDS Malignancies Consortium Clinical Trials 010 and 034

From the Weill Cornell Medical College; Memorial Sloan-Kettering Cancer Center; Albert Einstein Comprehensive Cancer Center, New York, NY; University of Arkansas for Medical Sciences, Little Rock, AR; Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Headington, Oxford, United Kingdom; University of California–San Francisco, San Francisco, CA; and National Cancer Institute, National Institutes of Health, Washington, DC.

Corresponding author: Ethel Cesarman, MD, PhD, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065; e-mail: ecesarm{at}med.cornell.edu.

Purpose Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis.

Patients and Methods We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts.

Results The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL.

Conclusion These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.

Supported by Grant No. CA-121947 from the National Cancer Institute to the AIDS Malignancy Consortium. A.H.B. is supported by the Leukaemia Research Fund, United Kingdom.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00049036 [ClinicalTrials.gov] and NCT00003595 [ClinicalTrials.gov] .

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