Microlocalization and clinical significance of stabilin-1+ macrophages in treatment-naïve patients with urothelial carcinoma of the bladder

Abstract

Emerging evidence has shown that macrophages (Mφs) at different tumor sites have diverse clinical attributes. Stabilin-1 is a multi-functional scavenger marker for specialized tumor-associated Mφs. This study investigates the relationship between the density and microlocalization of stabilin-1 + Mφs within tumors and the clinical outcomes of patients with urothelial carcinoma of the bladder (UCB). In this retrospective study, 283 UCB patients who received radical cystectomy or transurethral resection were examined. Immunohistochemistry and immunofluorescence analyses were used to colocalize the expression of stabilin-1 with other markers for Mφs (CD14, CD68, CD163, and CD206). Kaplan–Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS) and recurrence-free survival (RFS). In UCB tissues, stabilin-1 was primarily expressed on Mφs, as evident from triple immunofluorescence staining for stabilin-1 and Mφ markers. Stabilin-1 + Mφs were often more prominent in stromal regions rather than intratumoral regions in UCB tissues ( P < 0.0001). After dichotomization at the median cell density for stabilin-1 + Mφs, only intratumoral stabilin-1 + Mφ density was a predictor of poor OS ( P < 0.001) and RFS ( P = 0.026). Moreover, intratumoral stabilin-1 + Mφ density was positively associated with tumor stage ( P < 0.01) and histological grade ( P < 0.01), and emerged as an independent prognostic factor for OS (HR 2.371; P < 0.0001), but not for RFS (HR 1.491; P = 0.061). Our findings indicate that intratumoral stabilin-1 + Mφs could potentially be used as a pro-tumoral prognostic marker for UCB patients.