title: Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium.
abstract: Urothelial carcinoma in situ (CIS) is a high-grade neoplasm and an indicator of recurrence and progression that requires specific treatment. The distinction of CIS from flat non-neoplastic urothelium, in particular dysplasia, on the basis of histologic features is often difficult, and this study aims to validate cytokeratin 20 (CK20) and Ki-67 as discriminatory markers for this purpose. Immunostaining of these markers was applied to 26 cases of CIS, 14 atypia of unknown significance, 4 dysplasia, 6 normal, and 9 hyperplastic urothelium. CIS showed CK20 staining of deep urothelial cells in 23/26 CIS compared with restricted staining in surface cells in all non-neoplastic lesions. CIS had significantly increased Ki-67 index with a mean of 53.37% compared with that of non-neoplastic urothelium, which was <10% (P<0.0001). The proliferating cells were distributed randomly in CIS, whereas in non-neoplastic urothelium, staining was confined to the basal layer. Among the cases of atypia, 3/14 displayed deep staining for CK20 and 6/14 had elevated Ki-67 counts. In dysplasia similar findings were present in 1/4 and 2/4 cases, respectively. These findings suggest that CK20 and Ki-67 are objective markers to distinguish CIS from non-neoplastic urothelium. In cases of "atypia of unknown significance" and "dysplasia," positivity for both markers should raise the possibility of CIS or preneoplastic change and identify those cases for follow-up.
authors.affiliation: Department of Pathology, Genitourinary Institute, First Hospital of Peking University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Anthony S-Y
authors.initials: AS
authors.lastname: Leong
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000175:diagnosis*; D003937:Diagnosis, Differential; D006801:Humans; D053554:Keratin-20 / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*; D019459:Urothelium / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D053554:Keratin-20; D019394:Ki-67 Antigen