Assessment and significant of diploid-range epithelial populations in DNA aneuploid breast carcinomas using multi-parametric flow cytometry

Daniel W Visscher, Paula Sochacki, Susan Ottosen, Susan Wykes, John D. Crissman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 population, defined as cytokeratin-positive cells having a DNA content indistinguishable 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 normal 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 cases than in hyperdiploid (32%), hypodiploid (17%) or hypertetraploid cases (20%). The presence of diploid epithelial populations and/or multiple aneuploid stemlines correlated with histologic parameters, including an extensive intraductal component (unimodal - 4% vs. multi-modal - 57%, P = 0.001), heterogeneous differentiation (unimodal - 0% vs. multi-modal - 52%, P = 0.001), and multi-focal growth with residual interspersed benign tissue (unimodal - 8% vs. multimodal - 57%, P = 0.01). These data show that diploid-range epithelial cells are frequent in aneuploid 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-diploid measurements suggests the presence of diploid-range neoplastic stemlines which would be 'hidden' by contaminating host-derived cells in single parameter DNA histograms. Finally, the correlation of DNA content heterogeneity with distinctive histologic patterns of breast neoplasia implies that co-existing stemlines may have biological significance in the progression of some tumors.

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
JournalAnalytical Cellular Pathology
Volume8
Issue number4
StatePublished - Jun 1995
Externally publishedYes

Fingerprint

Aneuploidy
Diploidy
Flow Cytometry
Breast Neoplasms
DNA
Population
Keratin-20
Keratins
Neoplasms
Polyploidy
Tetraploidy
Fluorescein-5-isothiocyanate
Breast
Epithelium
Color
Epithelial Cells
Lymphocytes
Growth

Keywords

  • Breast carcinoma
  • Flow cytometry
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology

Cite this

Assessment and significant of diploid-range epithelial populations in DNA aneuploid breast carcinomas using multi-parametric flow cytometry. / Visscher, Daniel W; Sochacki, Paula; Ottosen, Susan; Wykes, Susan; Crissman, John D.

In: Analytical Cellular Pathology, Vol. 8, No. 4, 06.1995, p. 267-277.

Research output: Contribution to journalArticle

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abstract = "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 population, defined as cytokeratin-positive cells having a DNA content indistinguishable 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 normal 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 cases than in hyperdiploid (32{\%}), hypodiploid (17{\%}) or hypertetraploid cases (20{\%}). The presence of diploid epithelial populations and/or multiple aneuploid stemlines correlated with histologic parameters, including an extensive intraductal component (unimodal - 4{\%} vs. multi-modal - 57{\%}, P = 0.001), heterogeneous differentiation (unimodal - 0{\%} vs. multi-modal - 52{\%}, P = 0.001), and multi-focal growth with residual interspersed benign tissue (unimodal - 8{\%} vs. multimodal - 57{\%}, P = 0.01). These data show that diploid-range epithelial cells are frequent in aneuploid 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-diploid measurements suggests the presence of diploid-range neoplastic stemlines which would be 'hidden' by contaminating host-derived cells in single parameter DNA histograms. Finally, the correlation of DNA content heterogeneity with distinctive histologic patterns of breast neoplasia implies that co-existing stemlines may have biological significance in the progression of some tumors.",
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