High level of mature tumor-infiltrating dendritic cells predicts progression to muscle invasion in bladder cancer

Abstract

A prognostic value for tumor-associated macrophages (TAMs) and tumor-infiltrating dendritic cells (TIDCs) has been reported in many human cancers. The objective of this study is to determine the prognostic value of CD83(+) mature TIDCs and CD68(+) TAMs in non-muscle-invasive bladder cancer at first diagnosis. Immunohistochemistry staining was performed with anti-CD68 and anti-CD83 monoclonal antibodies on tissue sections from 93 formalin-fixed, paraffin-embedded tissue blocks from pTa and pT1 bladder tumors. A scoring index based on the average density of observed positive cells in the papillary axis, the stroma, lymphoid aggregates, and into tumor foci was calculated for each patient. Comparison of baseline characteristics with marker levels was done using Pearson χ(2) or Fisher exact test. Kaplan-Meier analyses and Cox regression models were fitted to evaluate the prognostic value of TIDCs and TAMs. The absence of both CD68(+) TAMs and CD83(+) TIDCs was associated with tumor recurrence. The presence of TIDCs was associated with a significant risk of progression to muscle-invasive cancer (hazard ratio, 8.253; P = .0179). Patients were risk stratified using age and TIDC score. Patients 70 years or older with a high score of TIDCs had a 56% progression-free survival after 6 years compared with 94% for patients younger than 70 years with a low score of TIDCs. None of 20 patients with a low score of TAMs progressed. These data indicate that the presence of mature TIDCs and possibly TAMs may help risk-stratify patients at the time of first diagnosis of non-muscle-invasive bladder cancer and may be useful in tailoring follow-up and treatment strategies.

Keywords: BCG; Bacillus Calmette-Guérin; CI; CIS; DC; Dendritic cells; EORTC; European Organization for Research and Treatment of Cancer; HR; Macrophages; Non–muscle-invasive bladder cancer; Prognostic; TAM; TIDC; TUR; Tumor infiltration; carcinoma in situ; confidence interval; dendritic cells; hazard ratio; transurethral resection; tumor-associated macrophage; tumor-infiltrating dendritic cells.