Nectin-4 immunohistochemistry distinguishes urothelial carcinoma in situ from reactive urothelium

Nectin-4 has been reported to be frequently overexpressed in urothelial carcinoma; however, its expression and diagnostic utility in urothelial carcinoma in situ (CIS) have not been systematically evaluated. In this study, we compared Nectin-4 expression in 50 cases of urothelial CIS and 50 cases of normal or reactive urothelium. Whole sections were immunohistochemically stained for Nectin-4, CK20 and p53, and staining results were evaluated using the H-score. Membranous Nectin-4 expression was significantly higher in urothelial CIS than in normal or reactive urothelium (p < 0.001) (24/50). A mutation type p53 immunohistochemical pattern was observed in 19/50 CIS cases (38%), while all benign urothelial samples displayed a wild-type pattern. Aberrant CK20 expression was present in 34/50 CIS cases (68%). The combination of CK20 and Nectin-4 detected 74% of CIS cases, exceeding the detection rate obtained with the commonly used CK20/p53 combination (62%) and the Nectin-4/p53 combination (68%). These findings indicate that Nectin-4 is frequently overexpressed in urothelial CIS and may serve as a useful adjunct immunohistochemical marker, particularly in combination with CK20, for the diagnosis of urothelial CIS.