p16/Ki-67 dual labeling and urinary cytology results according to the New Paris System for Reporting Urinary Cytology: Impact of extended follow-up.

BACKGROUND: Overexpression of p16INK4a has been identified in urothelial malignancies both cytologically and histologically. In addition, p16/Ki-67 dual labeling has been shown to identify high-grade urothelial cancer cells and some progression cases within a 12-month delay. The Paris System for Reporting Urinary Cytology (TPS) was published in late 2015. Its aim is to clarify the criteria for diagnosing or, conversely, excluding high-grade urothelial carcinoma (HGUC).

METHODS: Dual labeling was performed on archived ThinPrep-based Papanicolaou slides. A total of 208 samples (negative for high-grade urothelial carcinoma [NHGUC], 59; consistent with low-grade urothelial neoplasia [LGUN], 24; atypical urothelial cells [AUC], 15; and suspicious for or showing HGUC, 110) were analyzed for p16/Ki-67 after reclassification according to TPS. We assessed the oncologic status of the patients with cystoscopy, urinary cytology, histology, and prolonged 36-month follow-up data.

RESULTS: The sensitivity of p16/Ki-67 for life-threatening lesions was not different from that of urinary cytology (82.8% vs 83.6%; P = 1). However, among patients with samples classified as NHGUC and AUC, disease-free survival was significantly shorter for dual-labeled cases versus cases with negative dual labeling (P < .0001). The same tendency was observed in patients with histologically proven LGUN (P < .0001). As for specificity in patients with negative cystoscopy and cytology combined, prolonged follow-up showed 90% overall survival at 24 months.

CONCLUSIONS: A long-term evaluation of p16/Ki-67 dual labeling may identify HGUC and progression in cases with negative/low-grade urinary cytology results, and there are potential implications for the clinical management of patients after the conservative treatment of non-muscle-invasive urothelial carcinoma. Cancer Cytopathol 2017;125:552-62. © 2017 American Cancer Society.