CHROMATIN ORGANIZATION AND BREAST-CANCER PROGNOSIS - 2-DIMENSIONAL AND 3-DIMENSIONAL IMAGE-ANALYSIS

Background. The assessment of breast cancer prognosis still relies on clinical staging and histologic grading. Among the different prognosti c parameters, attention has been focused on features of chromatin stru cture. Although data from two-dimensional (2-D) analysis of chromatin structure show significant correlation with the survival, their biolog ic interpretation remains difficult. In this respect, insights into th e spatial organization of chromatin appear important. Methods. The aut hors performed computerized three-dimensional (3-D) reconstructions of Feulgen-stained tumor cell nuclei, correlating the results with those of 2-D image analysis. Forty-nine ductal-invasive carcinomas, with 10 -18 years follow-up were investigated. Results. The 2-D analysis demon strated that along with nuclear size and shape, chromatin features suc h as marginal concentration of condensed chromatin are of prognostic i mportance. As 3-D analysis revealed, chromatin changes concern ordered organization and were associated with the increase of spatial entropy .Conclusions. The 3-D description of chromatin structure by means of s patial models provides evidence that tumor aggressiveness correlates w ith events of clustering and randomization. These indicate disturbance s of ordered chromatin organization.