Utility of cytokeratin 20 and Ki-67 as markers of urothelial dysplasia

Reactive urothelial atypia (RUA) can be difficult to differentiate from dysplastic urothelium. The goal was to evaluate the efficacy of cytokeratin 20 (CK20), Ki-67 and E-cadherin (E-Cad) in this regard. Fifty carcinoma in situ (CIS) cases, 50 non-neoplastic urothelia (25 normal, 25 reactive urothelial atypia (RUA)) and 17 atypia of unknown significance (AUS) cases were evaluated. All cases were stained with monoclonal antibodies against Ki-67, CK20 and E-Cad. All (100%) normal urothelia showed normal staining patterns. In the CIS group, 86%, 82% and 20% of cases showed abnormal expression with CK20, Ki-67 and E-Cad, respectively. Both Ki-67 and CK20 were positive in 68% of cases. In the RUA group, 96%, 72% and 100% of cases showed normal expression patterns with CK20, Ki-67 and E-Cad, respectively. Of 28% RUA cases with increased Ki-67, none demonstrated abnormal CK20 or E-Cad expression. In the AUS group, 47% demonstrated abnormal CK20 and increased Ki-67 expression, suggestive of urothelial dysplasia/CIS, 29% were negative with both, suggestive of RUA, and the remaining 24% cases could not be resolved. In summary, abnormal CK20 is a useful adjunct to morphology for confirming dysplasia. Ki-67 by itself is a less reliable marker of dysplasia. E-Cad is not a useful marker in this setting.