Differential Diagnosis of Urothelial Carcinoma in Situ from Non-Neoplastic Urothelia: Analysis of CK20, CD44, P53 and Ki67

Background: Flat urothelial lesions comprise a spectrum of morphologic changes rangingfrom reactive atypia to carcinoma in situ (CIS). Urothelial dysplasia and CIS are related torecurrence and progression of urothelial carcinoma. Distinguishing CIS and dysplasia fromreactive atypia is often difficult on the basis of histolopathogical features alone. Usingdifferent immunohistochemical markers such as Cytokeratin 20 (CK20), CD 44, p53, and Ki-67 are recommended for differential diagnosis. The aim of the present study was to evaluatethe immunohistochemical pattern of these antibodies to differentiate different flat urotheliallesions.Methods: In a cross sectional study three groups of bladder biopsy specimens were evaluated:20 with Reactive urothelial lesions, 20 samples, histologically diagnosed as CIS, and 20samples which were morphologically normal looking. Immunohistochemical staining ofCK20, p53, CD44 and Ki-67 markers performed on paraffin-embedded blocks.Results: CK20 was full thickness positive in 15 (75%) CIS samples and were negative in allsamples of the normal and reactive groups (P< 0.001). CD44 was positive in 2 (10%) cases ofCIS group and 17 (85%) in the reactive group; this marker was negative in all of normalsamples (P<0.001). P53 was positive in 12 (60%) samples of CIS group and were negative inall samples of the normal and reactive groups (P< 0.001). Ki67 was positive in 13 (65%)samples of CIS group and 1 (5%) sample in the reactive group. This marker was negative inall samples of the normal group (P<0.001).Conclusions: These results support from this issue that CK20, CD44, P53 and Ki67 are usefulfor distinguishing of CIS from reactive and normal samples. Although they should be used ina panel including at least three markers. Correlation with the morphologic features is alwaysnecessary.