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

PURPOSE: 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). 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 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). RESULTS: 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). CONCLUSIONS: Our findings indicate that intratumoral stabilin-1(+) Mφs could potentially be used as a pro-tumoral prognostic marker for UCB patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00345-019-02853-0) contains supplementary material, which is available to authorized users.