Uroplakin II outperforms uroplakin III in diagnostically challenging settings

Aims We performed a head‐to‐head comparison of an antibody against uroplakin III ( UP 3) and a new uroplakin II ( UP 2) antibody that remains untested in diagnostically challenging settings. Methods and results We immunostained high‐grade bladder neck carcinomas ( n  =   35), high‐grade upper tract urothelial carcinomas ( UC ) and renal carcinomas ( n  =   85), metastases of UC ( n =  30) and a multicancer tissue microarray ( n  =   88) for UP 3 and UP 2, and scored staining intensity and proportion. UP 3 showed membranous plaque‐like expression, while UP 2 staining showed both membranous and cytoplasmic positivity. Significantly greater intensity ( P  =   0.003) and proportion ( P  =   0.03) of staining was noted for UP 2 among bladder neck lesions, with UP 2 staining showing greater sensitivity (63% versus 19%) and similar specificity (95% versus 100%) for UC over prostate carcinoma ( P  =   0.02). Among upper tract lesions, UP 2 staining showed greater intensity and proportion than UP 3 (both P  < 0.001), including improved sensitivity (68% versus 23%) and equal specificity (both 100%) for UC ( P  =   0.006). Among UC metastases, UP 2 staining showed greater intensity and proportion (both P  <   0.001) with higher sensitivity (73% versus 37%, respectively, P  =   0.001). Of 88 additional cases tested, no non‐urothelial cases stained for either UP . Conclusions The UP 2 antibody outperforms the UP 3 antibody, including in diagnostically challenging settings, and is a useful addition to the armamentarium of biomarkers for UC .