title: p16 INK4a overexpression and p16/Ki-67 dual labeling versus conventional urinary cytology in the evaluation of urothelial carcinoma.
abstract: 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). p16(INK4a) positivity was assessed in 171 of the 216 cases (79.2%) and in 93 of 99 high-grade cases with positive cytology (93.9%). Coexpression of p16/Ki-67 in the same cells was observed in 119 of 216 cases (55.1%) and was noted in 18 of 51 cases of negative or papillary urothelial neoplasia of low malignant potential/low-grade tumor (35.3%) and in 80 of 101 high-grade tumors (79.2%) (P < .0001). Thirteen of 14 high-grade intraurothelial lesions (92.8%) were dual labeled. 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 = .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.
authors.affiliation: Hospices Civils de Lyon, Centre de Biologie et Pathologie Est, Hôpital Femme-Mère-Enfant, Lyon Bron, France; Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Piaton
authors.forename: Christian
authors.initials: C
authors.lastname: Carré
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Advenier
authors.forename: Myriam
authors.initials: M
authors.lastname: Decaussin-Petrucci
authors.forename: Florence
authors.initials: F
authors.lastname: Mège-Lechevallier
authors.forename: Philippe
authors.initials: P
authors.lastname: Lantier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Granier
authors.forename: Alain
authors.initials: A
authors.lastname: Ruffion
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003584:Cytological Techniques / Q000379:methods*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins
keywords: Ki-67; bladder; follow-up; p16INK4a; prognosis; urothelial carcinoma