title: Uroplakin II outperforms uroplakin III in diagnostically challenging settings.
abstract: OBJECTIVE
  We performed a head-to-head comparison of an antibody against uroplakin III (UP3) and a new uroplakin II (UP2) antibody that remains untested in diagnostically challenging settings.
  
  
  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 UP3 and UP2, and scored staining intensity and proportion. UP3 showed membranous plaque-like expression, while UP2 staining showed both membranous and cytoplasmic positivity. Significantly greater intensity (P = 0.003) and proportion (P = 0.03) of staining was noted for UP2 among bladder neck lesions, with UP2 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, UP2 staining showed greater intensity and proportion than UP3 (both P < 0.001), including improved sensitivity (68% versus 23%) and equal specificity (both 100%) for UC (P = 0.006). Among UC metastases, UP2 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 UP2 antibody outperforms the UP3 antibody, including in diagnostically challenging settings, and is a useful addition to the armamentarium of biomarkers for UC.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Smith
authors.forename: Sambit K
authors.initials: SK
authors.lastname: Mohanty
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
authors.forename: Elena
authors.initials: E
authors.lastname: Chang
authors.forename: Fai
authors.initials: F
authors.lastname: Chung
authors.forename: Jason C
authors.initials: JC
authors.lastname: Carvalho
authors.forename: Gladel P
authors.initials: GP
authors.lastname: Paner
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Luthringer
authors.forename: Mariza N
authors.initials: MN
authors.lastname: de Peralta-Ventrurina
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
mesh_terms: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D060170:Uroplakin II / Q000032:analysis*; D060171:Uroplakin III / Q000032:analysis*
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C554658:UPK2 protein, human; C554660:UPK3A protein, human; D060170:Uroplakin II; D060171:Uroplakin III
keywords: biomarkers; immunohistochemistry; uroplakin; urothelial carcinoma