A Paget's disease with urinary origin would express which markers?

• A. CK7, GCDFP, & CEA
• B. S100, HMB45, & Melan-A
• C. CK20, uroplakin II, & GATA3
• D. CK20, CDX-2, & CEA

Answer: (C)

Immunohistochemistry helps identify where Paget cells come from by which markers they express. If Paget’s disease originates in the urinary tract, the cells typically show urothelial differentiation: CK20, uroplakin II, and GATA3. CK20 is common in urothelial carcinomas, uroplakin II is a urothelium-specific protein, and GATA3 is a transcription factor that is a reliable marker for urothelial origin. This combination specifically supports urinary tract origin.

Markers like S100, HMB45, and Melan-A are associated with melanocytic lesions, so they would point to melanoma rather than urothelial Paget disease. A set with CDX-2 along with CK20 and CEA suggests intestinal/colorectal differentiation (CDX-2 is an intestinal marker), not urinary.

So the urinary-origin profile is CK20, uroplakin II, and GATA3 because it reflects true urothelial differentiation.