title: Interobserver reproducibility in determining p16 overexpression in cervical lesions : use of a combined scoring method.
abstract: OBJECTIVE
  To evaluate interobserver reproducibility of a combined scoring method for immunohistochemical interpretation of p16 overexpression in cervical lesions.
  
  
  METHODS
  p16 immunostaining was performed in cervical samples from 183 patients, including 69 normal, 42 low grade squamous intraepithelial lesions(LSIL), 36 high grade SIL (HSIL), and 36 squamous cell carcinomas(SCCAs). Each case was evaluated by a combined scoring method based on the percentage of positive cells (score 0-3), the intensity of staining (score 0-3), and the distribution pattern (score 0-2). Immunoexpression for p16 was considered as positive when the combined score was 4-8 and negative with a score of 0-3. Ten pathologists with varied experience in interpretating p16 immunostains evaluated each slide independently.
  
  
  RESULTS
  All normal cervical squamous epithelia (69/69) were uniformly negative for p16. All HSILs (36/36), all SCCAs (100/100), and all but one of the LSILs (40/41, 97.6%) showed positive expression. In 172 of 183 cases (93.9%), p16 interpretation was concordant with all pathologists. Eleven cases with discordant results included 10 LSILs and 1 normal mucosa sample. Percentage of agreement of each pathologist pair ranged from 96.7-100% (mean 98.1%) with mean kappa value of 0.96 (range 0.93-1.000).
  
  
  CONCLUSIONS
  The proposed combined scoring method shows good reproducibility among the participating pathologists and good correlation with the histologic diagnosis. This method may be a useful guide in the interpretation of p16 expression in cervical epithelial lesions.
authors.affiliation: Institute of Pathology, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand. songkhun@gmail.com
authors.forename: Songkhun
authors.initials: S
authors.lastname: Vinyuvat
authors.forename: Anant
authors.initials: A
authors.lastname: Karalak
authors.forename: Cheepsumon
authors.initials: C
authors.lastname: Suthipintawong
authors.forename: Kobkul
authors.initials: K
authors.lastname: Tungsinmunkong
authors.forename: Pilaiwan
authors.initials: P
authors.lastname: Kleebkaow
authors.forename: Prasert
authors.initials: P
authors.lastname: Trivijitsilp
authors.forename: Sumalee
authors.initials: S
authors.lastname: Siriaunkgul
authors.forename: Surang
authors.initials: S
authors.lastname: Triratanachat
authors.forename: Surapan
authors.initials: S
authors.lastname: Khunamornpong
authors.forename: Tuenjai
authors.initials: T
authors.lastname: Chuangsuwanich
authors.forename: Jongkolnee
authors.initials: J
authors.lastname: Settakorn
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000453:epidemiology / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging / Q000379:methods; D015588:Observer Variation; D015203:Reproducibility of Results; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000453:epidemiology / Q000473:pathology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000453:epidemiology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16