AgNOR cut-point to distinguish mild and moderate epithelial dysplasia


Amit Chattopadhyay PhD, MPH, MDS, BDS (Hons), Dip. Journ, DcFM, MSASMS, Asst. Prof., Department of Epidemiology; University of Kentucky College of Public Health, Room No. 209-C, 121 Washington Avenue, Lexington, KY 40536, USA. Tel: +1 859 257 5678 (ext.) 82226, Fax: +1 859 257 8811,


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).

Conclusion:  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.