Tumor-Associated Macrophages in Primary Testicular Diffuse Large B Cell Lymphoma
Randy D Gascoyne, King L Tan, Kerry J Savage, David Telio, Tawny Hung, Joseph M Connors, David W Scott, Christian Steidl, Graham W Slack. British Columbia Cancer Agency, Vancouver, Canada
Background: The tumor microenvironment plays an important role in diffuse large B cell lymphoma (DLBCL). Gene expression profiling of DLBCL patients treated with R-CHOP defines two stromal signatures; the prognostically favorable stromal-1 signature reflecting extracellular-matrix deposition and macrophage infiltration, and the prognostically unfavorable stromal-2 signature reflecting in part, blood vessel density. While CD68 is used as a pan macrophage marker (both M1 and M2 subtypes), CD163 is reported to be a marker of alternatively-activated (M2) macrophages, which promote tumor growth and associated with worse prognosis in some solid tumors. We investigated the prognostic significance of CD68 and CD163 IHC in primary testicular DLBCL.
Design: A tissue microarray was constructed using duplicate 1.0mm cores from diagnostic paraffin blocks of 85 patients with primary testicular DLBCL. For survival analysis, patients not treated with curative intent or were HIV-positive were excluded, leaving 66 patients; 35 treated with R-CHOP and 31 with CHOP-like chemotherapy. CD68 and CD163 IHC was performed and analyzed using computer image analysis (Aperio) and pathologist scoring. Optimum thresholds for CD68 and CD163 expression and survival were determined by X-tile. Survival analysis was determined by Kaplan-Meier method with differences evaluated by log-rank test.
Results: There was a significant correlation between Aperio and pathologist scores for CD68 (R=0.721, p<0.001) and CD163 (R=0.941, p<0.001). In patients treated with R-CHOP therapy, increased CD68 expression was significantly associated with inferior survival (Table1). Increased CD163 expression showed a trend towards inferior survival (OS p=0.076, PFS p=0.099). Patients with increased CD68 expression had significantly higher CD163 expression (median 46.5% vs 27.7%, p=0.005). Using the same threshold for CD68 and CD163 expression in R-CHOP treated patients, no significant association with outcome was seen for either CD68 or CD163 expression in patients treated with CHOP-like chemotherapy.
|5 year PFS||59%||17%||0.003|
|5 year OS||62%||17%||0.006|