Chromatin organization and breast cancer prognosis. Two-dimensional and three-dimensional image analysis.

BACKGROUND

The assessment of breast cancer prognosis still relies on clinical staging and histologic grading. Among the different prognostic parameters, attention has been focused on features of chromatin structure. Although data from two-dimensional (2-D) analysis of chromatin structure show significant correlation with the survival, their biologic interpretation remains difficult. In this respect, insights into the spatial organization of chromatin appear important.

METHODS

The authors 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 demonstrated that along with nuclear size and shape, chromatin features such as marginal concentration of condensed chromatin are of prognostic importance. 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 spatial models provides evidence that tumor aggressiveness correlates with events of clustering and randomization. These indicate disturbances of ordered chromatin organization.