Immunocytochemical staining for p53 and Ki-67 helps to characterise urothelial cells in urine cytology

Objective The presence of atypical cells in urine cytology is unsatisfactory for both cytologists and clinicians. The objective of this study was to test whether p53 and Ki‐67 immunostaining could improve urothelial carcinoma (UC) detection on urinary cytology. Methods A total of 196 urine samples were analysed, 142 from the bladder, 41 from the upper tract and 13 from ileal bladder replacement. Cytology results were expressed as normal (N) (n = 81), atypia cannot exclude low‐grade UC (ALG) (n = 25), suspicious for high‐grade UC (SHG) (n = 39) and high‐grade UC (HG) (n = 51). Actual diagnoses were confirmed by histopathological analysis, cystoscopic examination or follow‐up for at least 1 year. Immunocytochemistry performed on CytoSpin™ slides allowed the determination of the percentage of positive cells with p53 and Ki‐67. Results The median percentage values [first to third quartile] of p53 and Ki‐67 were 0 [0–5] and 0 [0–1] for N cytology, 5 [0–40] and 2 [1–10] for ALG, 10 [0–30] and 6 [3–25] for SHG, and 30 [10–80] and 20 [10–30] for HG, respectively. Statistically higher values were observed for both tests (P < 0.001) in positive cytologies (ALG, SHG and HG). The optimal cut‐offs were 5% for p53 and 3% for Ki‐67. The sensitivity and specificity for the detection of all UC were 86.4% and 76.7% for cytology alone, 81.3% and 93.2% for cytology and p53, 75.7% and 88% for cytology and Ki‐67, and 68.9% and 97.5% for cytology, p53 and Ki‐67, respectively. Conclusion Using p53 and/or Ki‐67 in addition to cytology increases the specificity without penalising the sensitivity. In this study, immunocytochemistry with p53 and Ki‐67 was performed on 196 urine samples. Using cut‐offs of 5% positive cells for p53 and 3% for Ki‐67 increases specificity for the detection of urothelial carcinomas. This is of particular interest for the cytological diagnosis of urothelial tumors arising in the upper tract.