Evaluation of the prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma

Abstract

Background

Few biomarkers have been identified as prognostic factors in patients with primary central nervous system lymphoma (PCNSL).

Aims : To investigated the prognostic role of the tumor microenvironment, including CD68+ tumor-associated macrophages (TAMs) and FoxP3+ regulatory T-cells (Tregs) in patients with PCNSL.

Methods : We studied the immunohistochemical expression of CD68 and FoxP3 using formalin-fixed paraffin-embedded tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. The cut-off values for CD68+ TAMs and FoxP3+ Tregs were evaluated by the area under the receiver operating characteristic curve. We established cut-off values of 55 cells/high power field (HPF) for CD68 and 15 cells/HPF for FoxP3.

Results : The median age of the patients was 57 (range, 33-79) years and the median follow-up for survivors was 21.3 (range 1.2-128.5) months. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients underwent upfront autologous stem cell transplantation (ASCT) after a median of 4 (range, 2-4) cycles of HD-MTX-based chemotherapy. High expression of CD68 or FoxP3 was observed in 10 patients, respectively. High CD68 expression was associated with an inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (Hazard ratio [HR] 3.48, 95% confidential interval [CI]: 1.17-10.34, P=0.025, and HR 4.57, 95% CI: 1.81-11.56, P=0.006, respectively). In the non-upfront ASCT cohort (N=60), high CD68 expression was also associated with an inferior OS and PFS in multivariate analysis (P=0.017 and P=0.001, respectively). However, high CD68 expression was not associated with OS nor PFS in the upfront ASCT cohort (P=0.417 and P=0.951, respectively). The expression of FoxP3 was not significantly associated with survival in this study.

Summary / Conclusion : We identified a prognostic role for high CD68 expression in patients with PCNSL, and determined that consolidation treatment with upfront ASCT might overcome the negative impact of high CD68 expression in PCNSL.