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 uroth elial pTa and pTl tumors (8 papillomas, 8 neoplasms of low malignant potent ial, and 42 low-grade and 62 high-grade carcinomas) were immunostained by u sing CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression In stage with CK20 and CD44 immunoreac tivity were assessed, WHO/ISUP grade correlated with tumor stage (P < 0.005 ), recurrence (P = 0.02), and progression in stage (P = 0.031). Normal urot helium showed CK20 immunoreactivity restricted to a few umbrella cells. Exp ression of CD44 in normal urothelium was restricted to the basal cell layer . Loss of CD44 immunoreactivity and increasing CK20 positivity were signifi cantly associated with increasing tumor grade and stage (P < 0.005). An inv erse relationship was observed in the staining patterns of CK20 and CD44 wi thin individual cases, as wed as In the aggregate data, with 79.2% of tumor s with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 a nd CD44 immunoreactivity are significantly related to the WHO/ISUP grade an d to each other, and our data suggest their potential combined utility in p redicting biologic behavior In patients with papillary urothelial pTa and p Tl neoplasms.