title: p16/Ki-67 dual labeling and urinary cytology results according to the New Paris System for Reporting Urinary Cytology: Impact of extended follow-up.
abstract: BACKGROUND
  Overexpression of p16INK4ahas 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.
authors.affiliation: Centre de Pathologie Est, Hôpitaux de Lyon, Hôpital Femme-Mère-Enfant, Bron, France.|Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Piaton
authors.affiliation: Université Claude Bernard Lyon 1, Lyon, France.|Service de Médecine Légale, Lyon, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Advenier
authors.affiliation: Roche Diagnostics France, Meylan, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Carré
authors.affiliation: UMR INSERM U 1052/CNRS 5286, Université Claude Bernard Lyon, 1, France.|Centre de Pathologie Sud, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Decaussin-Petrucci
authors.affiliation: Université Claude Bernard Lyon 1, Lyon, France.|Service d'Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Mège-Lechevallier
authors.affiliation: Centre de Pathologie Est, Hôpitaux de Lyon, Hôpital Femme-Mère-Enfant, Bron, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Hutin
authors.affiliation: Centre de Pathologie Est, Hôpitaux de Lyon, Hôpital Femme-Mère-Enfant, Bron, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Nennig
authors.affiliation: Université Claude Bernard Lyon 1, Lyon, France.|Service d'Urologie, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Colombel
authors.affiliation: Université Claude Bernard Lyon 1, Lyon, France.|Service d'Urologie, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Ruffion
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D003558:Cystoscopy / Q000379:methods; D003581:Cytodiagnosis / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005602:France; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen
keywords: Ki-67; bladder; disease-free survival; p16INK4a; prognosis; urinary cytology; urothelial carcinoma