A Newly Developed Uroplakin II Antibody With Increased Sensitivity in Urothelial Carcinoma of the Bladder

• DOI: 10.5858/arpa.2013-0221-oa
• Publication Date: 2014-06-30T19:06:14Z
• Authors: Laura L. Hoang; David E. Tacha; Weimin Qi; Charlie Yu; Ryan E. Bremer; Joseph Chu; Thomas S. Haas; Liang Cheng
• Keywords: Male; Carcinoma, Transitional Cell; Uroplakin III; Blotting, Western; Immunohistochemistry; 3. Good health; Antibodies, Monoclonal, Murine-Derived; Mice; 03 medical and health sciences; 0302 clinical medicine; Urinary Bladder Neoplasms; Antibody Specificity; Pregnancy; Uroplakin II; Biomarkers, Tumor; Animals; Humans; Female; Tissue Distribution; Urothelium

Context.—Uroplakin II is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. Studies have shown uroplakin II messenger RNA to be expressed in bladder cancer tissues and peripheral blood of patients with urothelial carcinoma. Little is known about the protein expression of uroplakin II in urothelial carcinoma, possibly because of the absence of a commercially available uroplakin II antibody. Pathologists have used the uroplakin III antibody (AU1) to identify tumors of urothelial origin; however, the use of AU1 is limited because of its poor sensitivity. Objectives.—To evaluate a newly developed mouse monoclonal uroplakin II antibody (BC21) in urothelial carcinoma and to compare it with previously developed mouse monoclonal uroplakin III (BC17 and AU1). Design.—Uroplakin II and III antibodies were optimized for staining using a horseradish peroxidase-polymer detection system and were visualized with 3,3′-diaminobenzidine. Results.—BC21, BC17, and AU1 demonstrated sensitivities in urothelial carcinoma of the bladder of 79% (44 of 56), 55% (31 of 56) (P = .002), and 34% (19 of 56) (P < .001), respectively. Subsequently, the increased staining sensitivity and intensity of BC21, compared with BC17, was validated in a larger study (134 of 174; 77% and 94 of 174; 54%, respectively) (P < .001). BC21 was found to be highly specific when evaluated in various normal and neoplastic tissues, including prostatic and renal carcinomas. Conclusions.—The mouse monoclonal uroplakin II antibody (BC21) demonstrated superior sensitivity and specificity in urothelial carcinoma, compared with uroplakin III (BC17 and AU1), suggesting its advantages in the differential diagnosis of urothelial carcinoma and in the detection of tumors of unknown origin.