Silver-Stained Nucleolar Organizer Regions in Normal and Dysplastic Cervical Lesions: Correlation with DNA Ploidy and S-Phase Fraction by Flow Cytometry

Abstract

Objectives: To investigate the prognostic significance of DNA ploidy and silver-stained nucleolar organizer regions (AgNOR), their relation to the cytological grades of cervical dysplasia and correlation of cells in the S-phase of the cell cycle and DNA ploidy with AgNOR count. Methods: Multiparametric DNA flow-cytometric analysis and AgNOR count were performed on cervical smear samples, cytologically diagnosed as normal (n = 196), atypical squamous cells of unknown significance (ASCUS, n = 98) and various grades of cervical dysplasia (n = 127). Results: Among the cytological grade, aneuploid cases from low-grade squamous intraepithelial lesion (mild) and high-grade squamous intraepithelial lesion (moderate and severe) groups were showing high AgNOR counts (ranges 4.33–5.86 and 5.91–7.42, respectively). Aneuploid cases from the ASCUS group also presented high AgNOR (range 3.72–4.93). The high percentage of cells in the S-phase (>12%) correlated with these 2 parameters in the ASCUS and dysplasia groups. After grouping the cases into those with high (>4.0) and low (<4.0) AgNOR counts, significant correlations in the group with high AgNOR count with DNA ploidy, S-phase and cytological grade were recorded (p < 0.001). Results obtained from follow-up study revealed that cases with aneuploidy, high AgNOR count and S-phase fraction presented with a progressive trend of disease. Conclusions: Thus, the study shows that high AgNOR count, S-phase fraction and aneuploid DNA have prognostic significance in the early detection of cervical cancer.