We conclude that the new subcategories could help to standardize urine cytopathology reports and contribute to the patient's management, provided it is validated by multicentric studies.

BACKGROUND: Taking into consideration the known overexpression of p16 INK4a in histologically demonstrated high-grade urothelial malignancies, the objective of the current study was to examine the value of p16 INK4a overexpression and of p16/Ki-67 dual labeling versus urinary cytology in the detection of urothelial lesions. METHODS: Immunolabeling was performed on demounted and destained Papanicolaou slides after liquid-based ThinPrep processing. Actual diagnoses were ascertained by cystoscopy controls and histopathology. Negative cases, papillary urothelial neoplasia of low malignant potential/low-grade tumor, and high-grade lesions were considered separately. RESULTS: A total of 216 urine samples were collected from new patients with symptoms who were referred for cystoscopy (92 cases) or patients who were being followed after conservative treatment for lesions involving the bladder (117 cases) or the upper urinary tract (7 cases). When high-grade tumors, disease progression (increased grade, muscle infiltration, and extension into the upper urinary tract), and cancer-related death were grouped together as an endpoint, dual labeling demonstrated a sensitivity that was slightly higher than that of urinary cytology (82.5% vs 80.8%; P 5.8), with 94.9% overall specificity. CONCLUSIONS: When applied to the search for high-grade and aggressive disease, p16/Ki-67 dual labeling and urinary cytology appear to demonstrate comparable performance. Cancer (Cancer Cytopathol) 2014;122:211-20.

The data show that p16(INK4a) /Ki-67 co-expression allows most HG cancer cells to be detected initially and in the follow-up period. Additional studies are needed in order to determine whether dual labelling can be used as a triage tool for atypical urothelial cells in the urine.