p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia.

Academic Article


  • OBJECTIVES: 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. MATERIALS AND 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.
  • Keywords

  • Adult, Aged, Aged, 80 and over, Antigens, Neoplasm, Anus Neoplasms, Biopsy, Carcinoma in Situ, Clinical Competence, DNA, Neoplasm, Diagnosis, Differential, Female, Gene Expression Regulation, Neoplastic, Genes, p16, Humans, Male, Middle Aged, Observer Variation, Retrospective Studies
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23138169
  • Author List

  • Bean SM; Meara RS; Vollmer RT; Conner MG; Crowe DR; Novak L; Eltoum IA; Robboy SJ; Chhieng DC
  • Start Page

  • 145
  • End Page

  • 153
  • Volume

  • 13
  • Issue

  • 3