title: Immunohistochemical detection of p16INK4a in liquid-based cytology specimens on cell block sections.
abstract: BACKGROUND
  Colposcopy biopsy procedure is a standard recommendation for atypical squamous cell cannot exclude high-grade lesion (ASC-H) in abnormal Papanicolaou smears. p16 (p16INK4a), a cell cycle regulator, has been shown to be overexpressed in squamous dysplasia. To further improve the diagnostic accuracy of the ASC-H Papanicolaou smear and to reduce unnecessary procedures, the authors evaluated the utility of immunodetection of p16 in liquid-based cytology specimens on cell blocks.
  
  
  METHODS
  Seventy-five liquid-based (SurePath; TriPath Imaging, Inc. Burlington, NC) cytology specimens were prepared for cell blocks. Three groups (G1, G2, and G3) of cases were included: G1 comprised 44 cases of ASC-H; G2, 14 cases of high-grade dysplasia; and G3, 17 negative/reactive cases. All cases in G1 were confirmed by cervical biopsy or Digene Hybrid Capture 2 (Digene, Gaithersburg, Md) human papilloma virus (HPV) testing. Immunodetection for p16 was performed on cell blocks.
  
  
  RESULTS
  In G1, 26 of 44 (59%) cases showed squamous dysplasia, with 14 high-grade squamous intraepithelial lesion (HSIL) cases. Twenty-two of 28 (79%) p16-positive cases were confirmed by surgical biopsy or HPV testing, with a diagnostic sensitivity of 85%, specificity of 67%, positive predictive value (PPV) of 79%, and negative predictive value (NPV) of 75%. Four cases with false-negative staining for p16 were identified. All 28 cases of HSIL (14 from G1 and 14 from G2) were positive for p16.
  
  
  CONCLUSIONS
  1) p16 is a sensitive marker to confirm the diagnosis of ASC-H on a cell block; 2) Multiple unstained slides with adequate cellularity can be obtained from each cell block; and 3) Additional markers can be used to further increase diagnostic sensitivity and specificity.
authors.affiliation: Department of Pathology, Lehigh Valley Hospital, Allentown, Pennsylvania, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.forename: Jianhui
authors.initials: J
authors.lastname: Shi
authors.forename: Myra
authors.initials: M
authors.lastname: Wilkerson
authors.forename: Yajue
authors.initials: Y
authors.lastname: Huang
authors.forename: Steven
authors.initials: S
authors.lastname: Meschter
authors.forename: William
authors.initials: W
authors.lastname: Dupree
authors.forename: Fan
authors.initials: F
authors.lastname: Lin
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003584:Cytological Techniques; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D065006:Papanicolaou Test; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16