Evaluation of the prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma
Authors
조현수
Issue Date
2015
Description
의과대학/석사
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.