title: Utility of cytokeratin 5/6, cytokeratin 20, and p16 in the diagnosis of reactive urothelial atypia and noninvasive component of urothelial neoplasia.
abstract: BACKGROUND
  The utility of cytokeratin (CK)5/6 in distinguishing reactive urothelial atypia (RA) from urothelial carcinoma in situ (CIS) and from noninvasive component of high-grade papillary urothelial carcinoma (PUC) is unknown.
  
  
  METHODS
  Twenty RA with or without papillary hyperplasia and 90 noninvasive components of neoplastic urothelial lesions were submitted for immunostaining with CK5/6, CK20, and p16.
  
  
  RESULTS
  Diffuse and strong reactivity involving the full or nearly full thickness of urothelium was observed with CK5/6 in 90% of RA cases. CK20 and p16 were negative in 90% and 85% of the RA cases, respectively. For CIS and noninvasive components of high-grade PUC without squamous differentiation, there was no CK5/6 staining or reactivity in the basal layer only. CK20 and p16 showed strong positivity in full thickness of urothelium in 75% to 85% of cases. CIS with weak/focal or negative reactivity for p16 or CK20 exhibited moderate cytologic atypia. Low-grade PUC displayed variable reactivity for CK5/6, CK20, and p16. Urothelial lesions with squamoid or basaloid features showed positive reactivity for CK5/6. Urothelial lesions with glandular differentiation showed negative reactivity for CK5/6.
  
  
  CONCLUSIONS
  Diffuse CK5/6 reactivity in RA and negative CK5/6 reactivity in CIS and PUC may be helpful in distinguishing between these 2 entities.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Allison
authors.initials: A
authors.lastname: Edgecombe
authors.forename: Bich N
authors.initials: BN
authors.lastname: Nguyen
authors.forename: Bojana
authors.initials: B
authors.lastname: Djordjevic
authors.forename: Eric C
authors.initials: EC
authors.lastname: Belanger
authors.forename: Kien T
authors.initials: KT
authors.lastname: Mai
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003937:Diagnosis, Differential; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000235:genetics*; D053555:Keratin-5 / Q000235:genetics*; D053553:Keratin-6 / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D053554:Keratin-20; D053555:Keratin-5; D053553:Keratin-6; D009363:Neoplasm Proteins