CD34⁺ fibrocytes in chronic cystitis and noninvasive and invasive urothelial carcinomas of the urinary bladder

CD34⁺ fibrocytes are constitutive elements of the connective tissue where they play a role in matrix synthesis and tumor-associated stromal remodeling. Secreted protein, acidic, and rich in cysteine (SPARC) is a pivotal mediator of stromal remodeling precipitated by invasive carcinomas. The present study was undertaken to investigate CD34⁺ fibrocytes in the stroma of the tumor-free urinary bladder, chronic cystitis, and urothelial carcinomas together with stromal expression of α-smooth muscle actin (α-SMA), CD117, and SPARC. In tumor-free urinary bladder and chronic cystitis, CD34⁺ fibrocytes were found in the deep lamina propria and tunica muscularis, whereas the superficial lamina propria disclosed a CD34-negative and α-SMA-positive fibrocyte-like cell. Invasive urothelial carcinomas revealed a complete loss of CD34⁺ fibrocytes and concomitant appearance of α-SMA-reactive myofibroblasts which showed strong expression of SPARC. CD117 expression of tumor-free and tumor-associated stroma revealed no differences. We in this study for the first time describe CD34⁺ fibrocytes in the urinary bladder and an up-to-now unknown population of α-SMA-positive fibrocytes exclusively occurring in the superficial lamina propria. Stromal remodeling associated with invasive carcinomas in the urinary bladder is characterized by a loss of CD34⁺ fibrocytes paralleled by a gain of α-SMA-positive myofibroblasts and increased expression of SPARC.