Which combination of biomarkers is used to confirm urothelial carcinoma?

• A. Uroplakins II & III, CK20
• B. HER2 and EGFR
• C. PSA and PAP
• D. S100 and HMB-45

Answer: (A)

Immunohistochemical profiling is used to identify a tumor’s origin by detecting tissue-specific proteins. Urothelial carcinoma is best confirmed when markers that are highly characteristic of urothelial cells are present. Uroplakins II and III are urothelium-specific transmembrane proteins expressed in the lining’s umbrella cells; their detection strongly indicates urothelial differentiation and a urothelial origin. Pairing these with CK20, a cytokeratin commonly expressed in urothelial epithelium, strengthens the diagnosis by providing a complementary urothelial signal. Together, this combination gives high specificity for urothelial carcinoma, making it the best choice for confirmation.

Other options involve markers that are not specific to urothelial tissue: HER2 and EGFR are broader oncogenic markers; PSA and PAP point to prostate cancer; S100 and HMB-45 are associated with melanoma and related tumors.