title: Diagnostic reproducibility of cervical intraepithelial neoplasia 3 and atrophy in menopausal women on hematoxylin and eosin, Ki-67, and p16 stained slides.
abstract: OBJECTIVE
  To establish diagnostic accuracy and reproducibility of a diagnosis of cervical intraepithelial neoplasia 3 (CIN 3) in menopausal women on routinely stained hematoxylin and eosin (H&E) slides and compare it to slides processed for p16 and Ki-67.
  
  
  METHODS
  Confirmed cases of CIN 3 and benign atrophic changes were reviewed independently by 4 pathologists. The samples were studied on separate occasions using H&E staining, p16, and Ki-67. Differences in sensitivity and specificity between reviewers or methods were tested for significance using the McNemar test, whereas differences in positive and negative predictive values were tested for significance using a marginal probability generalized linear model for agreement.
  
  
  RESULTS
  Sensitivity was high for H&E (93.3%-100%) and Ki-67 (93.3%-100%) and lower for p16 (70.0%-90.0%). Intraobserver variability was also lower for p16 (76.7% vs 90.0%, although this difference was not statistically significant, p = .219). p16 agreement, however, for CIN 3 is significantly lower than that for atrophy (76.7% vs 97.4%, p = .018).
  
  
  CONCLUSIONS
  Routine histopathologic diagnosis of CIN 3 in menopausal women is highly accurate and reproducible. Both H&E and Ki-67 are useful immunohistochemical stains in helping differentiate atrophy from high-grade cervical intraepithelial lesions in postmenopausal cervical biopsies. There may be more disagreement among readers using p16.
authors.affiliation: Department of Obstetrics and Gynecology, NYU School of Medicine, New York, NY, USA.
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Cremer
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Amy E
authors.initials: AE
authors.lastname: Alspach
authors.forename: Ira A
authors.initials: IA
authors.lastname: Shulman
authors.forename: Sarka
authors.initials: S
authors.lastname: Cernosek
authors.forename: Steve
authors.initials: S
authors.lastname: Tsai
authors.forename: Natask
authors.initials: N
authors.lastname: Kalichanda
authors.forename: Juan C
authors.initials: JC
authors.lastname: Felix
mesh_terms: D000368:Aged; D001284:Atrophy / Q000175:diagnosis*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008593:Menopause; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D010336:Pathology / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins