Malignancy-associated changes in the breast. Changes in chromatin distribution in epithelial cells in...

Malignancy-associated changes (MACs) have been described as subtle morphologic changes in normal-appearing tissues adjacent to or distant from malignant tumors. MACs might be applicable as a marker of occult malignancy, increased risk of subsequent carcinoma or recurrence of tumor after therapy. The aim of this study was to verify the existence of MACs in normal-appearing breast tissue adjacent to breast carcinoma. Image cytometry measurements were performed on 4-microns sections cut from formaldehyde-fixed tissue blocks and stained with thionin-SO2 following the Feulgen procedure. Morphologically normal appearing breast lobules were analyzed in patients with benign (20 cases) and malignant breast disease (23 invasive and 11 in situ tumors). The chromatin distribution features of the epithelial nuclei in normal-appearing breast lobules differed between patients with benign and malignant breast disease. Changes in nuclear features, detected in epithelial nuclei from normal-appearing lobules in breasts resected for carcinoma, were defined as MACs. The frequency of MAC nuclei was low in benign tissues, increased in tissues with ductal carcinoma in situ and highest in tissues with invasive carcinoma. Based on the measurements of nuclei in normal-appearing lobules, it was possible to discriminate between patients with benign breast disease and patients with invasive carcinoma in 86% of cases.