Abstract
Sarcomatoid urothelial carcinoma (SUC) is a rare histologic subtype with poor prognosis. While there is known intra-tumoral 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-beta levels were significantly higher in SUC than in CUC. Immunohistochemical analysis revealed consistently moderate to strong expression of CD163-positive antigen-presenting cells (APCs) in SUC regions, whereas CD68-positive APC expression was generally absent. Thus, in mixed histology SUC, the SUC component preferentially expressed CD163-positive APCs and fibroblasts compared to the CUC component. As CD163-positive APCs and fibroblasts are known to be tumor-promoting and immune-suppressive, this infiltration may contribute to epithelial to mesenchymal transition and other aggressive properties of SUC.