title: Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms.
abstract: OBJECTIVE
  The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer.
  
  
  METHODS
  The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin-eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases.
  
  
  RESULTS
  The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of high-grade lesions (cervical intraepithelial neoplasm - CIN - 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68.
  
  
  CONCLUSIONS
  Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry.
authors.affiliation: Master's Program in Health Sciences, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil.
authors.forename: Fernanda Lopes Pontes
authors.initials: FL
authors.lastname: de Melo
authors.affiliation: Pathological Anatomy Course, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carmen Lúcia Penteado
authors.initials: CL
authors.lastname: Lancellotti
authors.affiliation: Pathological Anatomy Course, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria Antonieta Longo Galvão
authors.initials: MA
authors.lastname: da Silva
mesh_terms: D000328:Adult; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D030361:Papillomavirus Infections; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen