Quantitative cytological assessment of Ki67 and AgNORs using computer-digitized image analysis of four clinicopathological breast lesions

Analysis of silver-stained proteins associated with nucleolar organiser reg ions (AgNORs) is proposed as a marker of cellular proliferation. This study describes the application of AgNORs and Ki67 in breast lesions. Sixty-one cases including fibroadenoma (FA), fibrocystic disease (FCD), duc tal carcinoma in situ (DCIS) and invasive carcinoma (IC) were studied by im age analysis to evaluate quantitative changes in AgNORs in both Ki67-positi ve, and Ki67-negative smears. The Ki67 index was assessed, Morphometric fea tures of cell nuclei and AgNORs were determined by digitized computer image analysis (Prodit 5.2). The growth fraction was 5.08 for FA, 5.71 for FCD 16.75 for DCIS and 23.26 for IC. The mean nuclear area was significantly higher in malignant cells t han those of fibroadenoma and fibrocystic disease. In Ki67-positive cells the total area, long axis and number of AgNORs incre ased progressively across disease groups. Eccentricity of AgNORs and AgNORs : nuclear area ratios were significantly increased in malignant breast lesi on in comparison with benign lesion in Ki67 positive cells. In Ki67 negative cells, the highest value of AgNORs was observed in DCIS. T he AgNORs: nuclear area ratio demonstrated a statistically significant tren d across the disease groups. This study demonstrates that the growth fraction, mean nuclear area and sel ected AgNORs features have potential for differentiating benign from malign ant breast tumours.