title: Predictive value of the combined p16 and Ki-67 immunocytochemistry in low-grade squamous intraepithelial lesions.
abstract: OBJECTIVE
  The reliability of cytological diagnoses, especially for low-grade squamous intraepithelial lesions (LSIL), is limited. This leads to uncertainty in patient management. The application of adjunctive biomarkers is meant to improve this situation. Therefore, we examined the prognostic value of p16/Ki-67 immunostaining of LSIL cytology specimens.
  
  
  METHODS
  We analyzed the p16(INK4a) and Ki-67 immunocytochemistry (CINtec® PLUS, dual stain) of 260 patients with LSIL. Cytology and dual-stain results were correlated with histology at the time of treatment or with cytological follow-up.
  
  
  RESULTS
  After an average duration of 24.9 months (1-58) and a histology rate of 36.2% [cervical intraepithelial neoplasia, grade 2 or higher (CIN2+) as positive], the statistical evaluation for cytology and dual stain resulted in a sensitivity of 98.3 and 90.0%, respectively, a specificity of 74.5% for dual stain, a positive predictive value (PPV) of 22.8 and 51.4%, and a negative predictive value (NPV) of 96.1% for dual stain.
  
  
  CONCLUSIONS
  The combined immunocytochemical investigation of p16(INK4a) and Ki-67 leads to a significantly better PPV and a very good NPV for CIN2+ in LSIL, especially in women 30 years of age and older. An objective individualized prognosis may not be achieved with p16(INK4a)/Ki-67. Statistical data from our study, however, indicate that patient management can be significantly improved by the application of combined p16/Ki-67 immunocytochemistry as an adjunct to cytology.
authors.affiliation: Institute of Pathology, Potsdam-Bornstedt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ziemke
authors.forename: Katrin
authors.initials: K
authors.lastname: Marquardt
authors.forename: Henrik
authors.initials: H
authors.lastname: Griesser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D003581:Cytodiagnosis; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen