A, Histologic microphotograph of urothelial carcinoma in situ (UCIS) shows loss of nuclear stratification, positivity for Cytokeratin 20 and p16INK4a as well as increased proliferative activity as indicated by Ki-67 immunostaining. B, Comparison between high-grade cervical intraepithelial neoplasia (CIN III, upper row) and UCIS (lower row) shows a comparable distribution of p16INK4a immunopositivity. C, Reverse hybridization blotting detects high-risk human papillomavirus (HPV) genotype 16 DNA in representative CIN III, but not in UCIS samples. D, Fluorescence-in-situ-hybridization (FISH) analysis shows no amplification of CDKN2A gene encoding for p16INK4a (orange) compared to control (centromere 9, green) in representative p16INK4a-positive UCIS. Scale bars as indicated.