Which IHC stain diminishes as tumorigenesis occurs in HGUC?

• A. CK7
• B. Uroplakins
• C. GATA3
• D. HMWCK

Answer: (B)

The key idea is that markers of urothelial differentiation change as the tumor becomes more malignant. Uroplakins are specialized proteins present on the apical umbrella cells of normal urothelium, signaling terminal urothelial differentiation. In high-grade urothelial carcinoma, the tumor loses this umbrella cell phenotype, so uroplakin expression decreases and staining becomes weaker or absent. This loss reflects dedifferentiation as tumorigenesis progresses, making uroplakins the stain that diminishes with higher-grade disease. The other markers—CK7, GATA3, and high molecular weight cytokeratin—are commonly retained in urothelial carcinomas and are used to identify urothelial lineage, so they do not show the same consistent decline with progression.