ASSESSMENT AND SIGNIFICANCE OF DIPLOID-RANGE EPITHELIAL POPULATIONS IN DNA ANEUPLOID BREAST CARCINOMAS USING MULTI-PARAMETRIC FLOW-CYTOMETRY

A 2-color (PI, cytokeratin - FITC) multi-parametric analysis of intact cells was used to reveal diploid-range epithelial populations by flow cytometry in 108 consecutive DNA aneuploid breast carcinomas. Thirty- eight tumors (35%) contained a significant diploid range epithelial po pulation, defined as cytokeratin-positive cells having a DNA content i ndistinguishable from that of endogenous lymphocytes and comprising at least 20% of all cytokeratin-positive cells. An additional 23 cases ( 21%) contained a minor diploid range epithelial population having a no rmal DNA content and comprising only 5-20% of all cytokeratin-positive cells. Multiple DNA aneuploid stemlines were present in 24 cases (22% ). Diploid-range populations were more frequent (91%) in tetraploid ca ses than in hyperdiploid (32%), hypodiploid (17%) or hypertetraploid c ases (20%). The presence of diploid epithelial populations and/or mult iple aneuploid stemlines correlated with histologic parameters, includ ing an extensive intraductal component (unimodal - 4% vs. multi-modal - 57%, P = 0.001), heterogeneous differentiation (unimodal - 0% vs. mu lti-modal - 52%, P = 0.001), and multi-focal growth with residual inte rspersed benign tissue (unimodal - 8% vs. multimodal - 57%, P = 0.01). These data show that diploid-range epithelial cells are frequent in a neuploid breast carcinomas analyzed by flow cytometry. In some tumors, these populations undoubtedly reflect the presence of residual benign epithelium. The numerical dominance of other histograms by near-diplo id measurements suggests the presence of diploid-range neoplastic stem lines which would be 'hidden' by contaminating host-derived cells in s ingle parameter DNA histograms. Finally, the correlation of DNA conten t heterogeneity with distinctive histologic patterns of breast neoplas ia implies that co-existing stemlines may have biological significance in the progression of some tumors.