title: Analysis of performance characteristics of five cell cycle-related immunohistochemical markers and human papillomavirus genotyping in the diagnosis of cervical squamous cell carcinoma precursor lesions.
abstract: OBJECTIVE
  To study the performance values of a set of five immunohistochemical markers involved in cell cycle regulation as a potential aid in the differential diagnosis between squamous intraepithelial lesions (SILs) and normal or benign conditions of the uterine cervix.
  
  
  METHODS
  Results from immunohistochemical evaluation of p16, cyclin D1, p53, Ki67, and ProEx C markers and human papillomavirus genotyping were collected from a previous study performed on 37 normal or benign cervices, 39 low grade SILs and 73 high grade SILs. A multivariate analysis was used to examine the specific diagnostic value of each marker and to ascertain those most relevant for SIL diagnosis. For markers with good data fit, sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, and integrated discrimination improvement, were calculated.
  
  
  RESULTS
  Among individual markers, ProEx C showed the best specificity; p16 displayed the highest sensitivity and area under receiver operating characteristic curve for SIL diagnosis. Integrated discrimination improvement demonstrated that the p16 plus ProEx C model has better discrimination capacity than p16 plus Ki67 or ProEx C plus Ki67.
  
  
  CONCLUSIONS
  Use of ProEx C alone or in combination with p16 could provide useful information for SIL diagnosis.
authors.affiliation: Molecular Pathology and Pharmacogenetics Group, Department of Internal Medicine, Santa María del Rosell University Hospital, Cartagena, Spain. pablo.conesa@carm.es
authors.forename: Pablo
authors.initials: P
authors.lastname: Conesa-Zamora
authors.forename: Javier
authors.initials: J
authors.lastname: Trujillo-Santos
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Orantes-Casado
authors.forename: Sebastián
authors.initials: S
authors.lastname: Ortiz-Reina
authors.forename: Daniel
authors.initials: D
authors.lastname: Torres-Moreno
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Guillermo
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2