Diagnostic and prognostic value of nucleolar organizer regions in normal epithelium, dysplasia, and squamous cell carcinoma of the oral cavity

Abstract

Nucleolar organizer regions (AgNORs) are associated with proliferative activity and represent a diagnostic aid and prognostic marker in several neoplastic entities. Sections from 51 T1-2 squamous cell carcinomas (SCC), 20 cases of dysplasia, and 8 specimens with normal epithelium were evaluated by 2 AgNOR counting methods: 1) the mean number of AgNORs per nucleus (mAgNOR) and 2) the percentages of nuclei with > 1, > 2, > 3, and > 4 AgNORs (pAgNOR > 1, pAgNOR > 2, pAgNOR > 3, and pAgNOR > 4, respectively). Both mAgNOR and pAgNOR counts enabled significant discrimination between normal epithelium and dysplasia (P < 0.0003) and between dysplasia and SCC (P < 0.0001). For SCC, no correlation was found between AgNOR counts and clinical classification. Univariate analysis using the log rank test showed that the overall means for mAgNOR and pAgNORs correlated with the disease free period and survival time (P < 0.0040). Patient age, gender, type of treatment, and T and N classification failed to predict the outcome. Multivariate analysis showed that pAgNOR > 1 (cutoff level of 88%) was the best discriminator regarding the disease free period and survival time (P = 0.0001 and P = 0.0076, respectively). AgNOR enumeration, in particular pAgNOR > 1, appears to be a useful tool in distinguishing between normal epithelium, dysplasia, and SCC of the oral cavity. In this study, AgNOR counts were strong prognostic markers for patients with SCC.