Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia.

The aim of this study was to assess the relationship of immunoreactivity of cytokeratin 20 (CK20) and CD44 across the spectrum of urothelial neoplasia using the WHO/ISUP consensus classification. A total of 120 papillary urothelial pTa and pT1 tumors (8 papillomas, 8 neoplasms of low malignant potential, and 42 low-grade and 62 high-grade carcinomas) were immunostained by using CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression in stage with CK20 and CD44 immunoreactivity were assessed. WHO/ISUP grade correlated with tumor stage (P < 0.005), recurrence (P = 0.02), and progression in stage (P = 0.031). Normal urothelium showed CK20 immunoreactivity restricted to a few umbrella cells. Expression of CD44 in normal urothelium was restricted to the basal cell layer. Loss of CD44 immunoreactivity and increasing CK20 positivity were significantly associated with increasing tumor grade and stage (P < 0.005). An inverse relationship was observed in the staining patterns of CK20 and CD44 within individual cases, as well as in the aggregate data, with 79.2% of tumors with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 and CD44 immunoreactivity are significantly related to the WHO/ISUP grade and to each other, and our data suggest their potential combined utility in predicting biologic behavior in patients with papillary urothelial pTa and pT1 neoplasms.