title: AgNOR cut-point to distinguish mild and moderate epithelial dysplasia.
abstract: BACKGROUND
  Distinguishing mild and moderate epithelial dysplasia is difficult and controversial. We demonstrated earlier that silver-stainable nucleolar organizer region (AgNOR) is a simple, inexpensive and quantifiable method which can standardize this distinction reliably.
  
  
  OBJECTIVE
  To establish a cut-point mean AgNOR count for epithelial dysplasia validated by bootstrapping.
  
  
  METHODS
  One hundred oral leukoplakia biopsies at Dr R. Ahmed Dental College, Kolkata, India, examined for epithelial dysplasia using standard method (gold standard) were assessed for their mean AgNOR counts. A cut-point was selected employing receiver operating characteristic (ROC) curve. This estimate was stabilized by 10 000 resamples (with replacement) using parametric and non-parametric bootstrap, a Monte Carlo statistical method, corrected for bias to estimate standard errors (SE) of cut-point.
  
  
  RESULTS
  Area under the curve (AUC) was 74%; non-parametric method suggested mean AgNOR cut-point = 2.42 AgNORs/nucleus; parametric method suggested cut-point = 2.57. The cut-point 95% confidence intervals (CIs) (bias corrected and accelerated) from parametric method (2.31; 2.66) was lower than non-parametric (2.43; 2.82).
  
  
  CONCLUSIONS
  Applying a conservative paradigm, taking the lowest of all bootstrap 95% CIs, we suggest that mean AgNOR count of 2.3 be used as a cut-point for distinguishing between mild and moderate dysplasia. This strategy will provide an inexpensive, meaningful, definitive, reproducible and consistent diagnostic test for epithelial dysplasia.
authors.affiliation: Department of Epidemiology, University of Kentucky College of Public Health, Lexington, KY 40536, USA. achat4@email.uky.edu
authors.forename: Amit
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Jay G
authors.initials: JG
authors.lastname: Ray
mesh_terms: D019540:Area Under Curve; D004847:Epithelial Cells / Q000473:pathology*; D006801:Humans; D007972:Leukoplakia, Oral / Q000473:pathology*; D009010:Monte Carlo Method; D009062:Mouth Neoplasms / Q000473:pathology*; D009697:Nucleolus Organizer Region / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016622:Silver Staining