title: Argentophilic nucleolus organizer region as a proliferation marker in cervical intraepithelial neoplasia grade 1 of the uterine cervix.
abstract: OBJECTIVE
  p16INK4a and argentophilic nucleolus organizer region (AgNOR) can be used as markers for progression of cervical intraepithelial neoplasia grade 1 (CIN1) of the uterine cervix. Our objective was to study the predictive value of the AgNOR technique as a progression marker of CIN1 and its correlation with p16INK4A.
  
  
  METHODS
  One uterine cervix biopsy from each of 75 patients with diagnosis of CIN1 was selected. All of these patients underwent a second biopsy, and these were also used for the study.
  
  
  RESULTS
  The second biopsies showed: regression (20 patients), persistent CIN1 (38 patients), progression to CIN2 (10 patients) and progression to CIN3 (seven patients). p16INK4A showed reactivity in 67 of the 75 first CIN1 biopsies: 12 of the 20 cases that cleared the lesions and the 55 cases with persistent or progressive lesions were positive for p16INK4a (specificity: 40%; sensitivity: 100%; positive predictive value [PPV]: 82%; negative predictive value [NPV]: 100%). Samples with AgNOR areas less than 3.0 μ(2) returned in all cases, but patients whose lesions persisted or progressed to CIN2/CIN3, showed AgNOR areas greater than 3.0 μ(2) in 50/55 cases (specificity: 100%; sensitivity: 91%; PPV: 100%; NPV: 80%).
  
  
  CONCLUSIONS
  p16INK4a is expressed in a high percentage of returning lesions. AgNOR might be a better marker of proliferation of CIN1 than p16INK4a (PPV = 100%), which means that a value greater than 3.0 μ(2) indicates the persistence or progression of the lesion. As its NPV is 80%, a value of AgNOR area less than 3.0 μ(2) in CIN1 leaves a margin of doubt about the future behavior of the lesion.
authors.affiliation: Department of Clinical Biochemistry, Leloir Institute Foundation - CONICET, Buenos Aires, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Guerra
authors.forename: Adriana Esther
authors.initials: AE
authors.lastname: Rocher
authors.forename: José
authors.initials: J
authors.lastname: Villacorta Hidalgo
authors.forename: Lilí
authors.initials: L
authors.lastname: Díaz
authors.forename: Susana
authors.initials: S
authors.lastname: Vighi
authors.forename: Lucía
authors.initials: L
authors.lastname: Cardinal
authors.forename: Silvio
authors.initials: S
authors.lastname: Tatti
authors.forename: Nicasio
authors.initials: N
authors.lastname: Cúneo
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Prat Gay
authors.forename: Gabriela
authors.initials: G
authors.lastname: Camporeale
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Palaoro
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009697:Nucleolus Organizer Region / Q000737:chemistry*; D012835:Silver Nitrate; D002583:Uterine Cervical Neoplasms / Q000737:chemistry*; D002578:Uterine Cervical Dysplasia / Q000737:chemistry*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012835:Silver Nitrate
keywords: argyrophilic nucleolar organizer region; cervical intraepithelial neoplasia grade 1; p16INK4a; progression of cervical lesions; uterine cervix