Journal
BLOOD
Volume 120, Issue 16, Pages 3280-3287Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-04-421057
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Funding
- Public Health Service [CA21115, CA23318, CA66636, CA17145, CA11083, CA32102, CA38926, CA77202, CA21076, CA77470]
- National Cancer Institute, National Institutes of Health
- Department of Health and Human Services
- Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research [TGT-53912]
- Cancer Research Society
- Michael Smith Foundation for Health Research
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Increased tumor-associated macrophages (TAMs) are reported to be associated with poor prognosis in classic Hodgkin lymphoma (CHL). We investigated the prognostic significance of TAMs in the E2496 Intergroup trial, a multicenter phase 3 randomized controlled trial comparing ABVD and Stanford V chemotherapy in locally extensive and advanced stage CHL. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tumor tissue and included 287 patients. Patients were randomly assigned into training (n = 143) and validation (n = 144) cohorts. Immunohistochemistry for CD68 and CD163, and in situ hybridization for EBV-encoded RNA were performed. CD68 and CD163 IHC were analyzed by computer image analysis; optimum thresholds for overall survival (OS) were determined in the training cohort and tested in the independent validation cohort. Increased CD68 and CD163 expression was significantly associated with inferior failure-free survival and OS in the validation cohort. Increased CD68 and CD163 expression was associated with increased age, EBV-encoded RNA positivity, and mixed cellularity subtype of CHL. Multivariate analysis in the validation cohort showed increased CD68 or CD163 expression to be significant independent predictors of inferior failure-free survival and OS. We demonstrate the prognostic significance of TAMs in locally extensive and advanced-stage CHL in a multicenter phase 3 randomized controlled clinical trial. (Blood. 2012;120(16):3280-3287)
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