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While there is known intra\u2010tumoral heterogeneity between individual SUC tumors, the relationship between sarcomatoid and conventional urothelial carcinoma (CUC) within the same patient is poorly understood. The objective of this study was to identify differences between the sarcomatoid and CUC tumor microenvironment components that may drive this aggressive phenotype. Using tissue microarrays from eight patient tumors with mixed CUC and SUC, we examined paired CUC, mixed urothelial carcinoma (UC) regions, and SUC using the Nanostring Digital Spatial Profiling platform. We found SUC and mixed UC had higher levels of stromal cells, predominately macrophages and fibroblasts, when compared with CUC within the same tumor. CD14, CD163, and transforming growth factor\u2010beta levels were significantly higher in SUC than in CUC. Immunohistochemical analysis revealed consistently moderate to strong expression of CD163\u2010positive antigen\u2010presenting cells (APCs) in SUC regions, whereas CD68\u2010positive APC expression was generally absent. Thus, in mixed histology SUC, the SUC component preferentially expressed CD163\u2010positive APCs and fibroblasts compared to the CUC component. As CD163\u2010positive APCs and fibroblasts are known to be tumor\u2010promoting and immune\u2010suppressive, this infiltration may contribute to epithelial to mesenchymal transition and other aggressive properties of SUC.<\/jats:p>","DOI":"10.1002\/2056-4538.70021","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T21:48:57Z","timestamp":1740001737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sarcomatoid areas of urothelial carcinoma are enriched for <scp>CD163<\/scp>\u2010positive antigen\u2010presenting cells"],"prefix":"10.1002","volume":"11","author":[{"suffix":"III","given":"Burles A","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Oncology The Johns Hopkins Medical Institutions  Baltimore Maryland USA"},{"name":"Department of Urology Johns Hopkins Greenberg Bladder Cancer Institute  Baltimore Maryland 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