title: p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia.
abstract: OBJECTIVE
  Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (H&E) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.
  
  
  METHODS
  Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed H&E alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.
  
  
  RESULTS
  Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using H&E diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for H&E/p16/Ki-67 combined were comparable to that of H&E alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, H&E/p16/Ki-67 combined, and H&E alone.
  
  
  CONCLUSIONS
  Interobserver agreement for diagnosis of AIN was fair when based solely on H&E preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with H&E, Ki-67, and H&E/p16/Ki-67 combined.
authors: Department of Pathology, Duke University Medical Center, Durham, NC, USA. sarah.bean@duke.edu
authors: Sarah M
authors: SM
authors: Bean
authors: Regina S
authors: RS
authors: Meara
authors: Robin T
authors: RT
authors: Vollmer
authors: Michael G
authors: MG
authors: Conner
authors: D Ralph
authors: DR
authors: Crowe
authors: Lea
authors: L
authors: Novak
authors: Isam A
authors: IA
authors: Eltoum
authors: Stanley J
authors: SJ
authors: Robboy
authors: David C
authors: DC
authors: Chhieng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D001706:Biopsy; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000276:immunology; D002983:Clinical Competence; D004273:DNA, Neoplasm / Q000032:analysis*; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D012189:Retrospective Studies
chemical_list: D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm