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

Purpose Emerging evidence has shown that macrophages (M phi s) at different tumor sites have diverse clinical attributes. Stabilin-1 is a multi-functional scavenger marker for specialized tumor-associated M phi s. This study investigates the relationship between the density and microlocalization of stabilin-1(+) M phi s within tumors and the clinical outcomes of patients with urothelial carcinoma of the bladder (UCB). Methods 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 M phi s (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). Results In UCB tissues, stabilin-1 was primarily expressed on M phi s, as evident from triple immunofluorescence staining for stabilin-1 and M phi markers. Stabilin-1(+) M phi s 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(+) M phi s, only intratumoral stabilin-1(+) M phi density was a predictor of poor OS (P < 0.001) and RFS (P = 0.026). Moreover, intratumoral stabilin-1(+) M phi 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). Conclusions Our findings indicate that intratumoral stabilin-1(+) M phi s could potentially be used as a pro-tumoral prognostic marker for UCB patients.