Epithelial-stromal interactions in tumors. A morphologic study of fibroepithelial tumors of the breast

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Abstract
Background and Methods. The known spatial interaction between normal breast epithelium and its surrounding stroma prompted an investigation of the spatial relationship between stromal mitoses and the epithelial component of fibroepithelial tumors of the breast. The authors applied a novel computerized morphometric technique to routinely processed histologic sections of 23 fibroepithelial tumors (13 fibroadenomas and 10 phyllodes tumors). The proportional area of epithelium in successive concentric annuli surrounding stromal mitoses was measured, and its distribution was compared with that around suitable control points. Results. The authors found that stromal mitotic activity in these tumors was significantly more likely to occur close to rather than remote from the epithelial component, with a significant excess of epithelium around mitoses compared with control points within a range of 79 microns. Essentially similar findings were obtained when randomly identified fibroblast nuclei were used as control points, thus obviating variations in stromal cell density with distance from epithelium as an explanation for the findings. Conclusions. These findings support the hypothesis that stromal growth in fibroepithelial tumors depends, to a variable extent, on the epithelial component. An interaction in the opposite direction (i.e., the stroma providing the growth support to the epithelium) also may occur, but this was not investigated. It is suggested that there is an interdependence of growth between the epithelial and stromal components in these tumors that explains their complex morphology and that stromal dependence on epithelium is lost with increasing malignancy of the stromal elements.