Immunohistochemical profile to distinguish urothelial from squamous differentiation in carcinomas of urothelial tract.

Urothelial neoplasms with squamous morphology raise the differential diagnosis between pure primary squamous cell carcinoma, urothelial carcinoma with squamous differentiation and secondary involvement by squamous cell carcinoma, for example, from uterine cervix. Accurate identification between these entities is critical due to differing prognosis and therapeutic strategies. We evaluated the utility of an immunohistochemical panel of 3 urothelial-associated antibodies (uroplakin III, S100P, and GATA3) and two squamous-associated antibodies (CK14 and desmoglein-3) in 50 primary urothelial neoplasms: 15 pure urothelial carcinomas, 12 pure squamous cell carcinomas and 23 urothelial carcinomas with squamous differentiation. Squamous differentiation was defined by intercellular bridges or evidence of keratinization. Pure squamous cell carcinomas were positive for CK14 (100%) and desmoglein-3 (75%), negative for GATA3 and uroplakin III; one case was S100P positive (9%). Pure urothelial carcinomas had an opposite pattern and were positive for S100P (93%), GATA3 (93%), and uroplakin III (67%) and were negative for desmoglein-3; CK 14 was positive in 27% of cases; 74% of urothelial carcinomas with squamous differentiation had expression of urothelial and squamous associated markers (S100P, 83%; GATA3, 35%; uroplakin III, 13%; CK14, 87%; and desmoglein-3, 70%), although reactivity for individual markers within some tumors did not always correspond with morphologic differentiation. Of the remaining 26%, 4 showed an overall "squamous" immunoprofile, whereas 2 cases showed a "urothelial" immunoprofile. Our study showed that a panel of five antibodies identifies squamous and urothelial differentiation in most instances suggesting potential diagnostic utility.