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The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association

Purpose: We aimed to assess the prognostic significance of follicular lymphoma–associated macrophages in the era of rituximab treatment and maintenance. Experimental Design: We applied immunohistochemistry for CD68 and CD163 to two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets. Results: An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset [5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort). Conclusions: CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received. Clin Cancer Res; 21(15); 3428–35. ©2015 AACR.