Analytical approaches relating genetic evolutionary pathways to prognostic factors

Journal Article · Fri Sep 01 04:00:00 EDT 1995 · Cytometry

DOI:https://doi.org/10.1002/cyto.990210107· OSTI ID:443397

Rohloff, A C; Sakach, J M; Shackney, S E ^[1]

---

1. Allegheny-Singer Research Inst., Pittsburgh, PA (United States)

Human solid tumors accumulate multiple genetic abnormalities as they progress to advanced stages. Multiparameter flow cytometry measurements of individual cells within each tumor may be useful in describing the genetic pathways taken by individual tumors during the course of their genetic evolution. In this paper, we analyzed correlated cell-by-cell measurements of cell DNA content, HER-2/neu protein content, and ras protein content obtained by multiparameter flow cytometry studies of primary breast cancers from 92 patients. These laboratory findings were correlated with established clinical prognostic factors for each patient at the time of diagnosis, using a stepwise multiple analysis of variance (MANOVA). The stepwise MANOVA successively splits a group of patients into two mutually exclusive dissimilar groups, selecting the clinical prognostic factor that is most effective in doing so. Using this criterion, formation of the first three groups that were judged most dissimilar on the cytometry parameters was based on the number of positive nodes at the time of diagnosis. We show that ploidy, HER-2/neu protein content, and ras protein content, as measured by multiple parameter flow cytometry, are correlated with nodal status and other known clinical prognostic factors. The cell-by-cell multiparameter data suggest that for some individual tumors there are multiple genetic evolutionary pathways. Multiple genetic evolutionary pathways are also suggested by the MANOVA analysis. Focusing on the identification and analysis of genetic evolutionary pathways within individual tumors and across patients appears to offer a promising approach for defining the prognosis of early cancers. 9 refs., 2 figs., 7 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 443397
• Journal Information: Cytometry, Journal Name: Cytometry Journal Issue: 1 Vol. 21; ISSN CYTODQ; ISSN 0196-4763
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL EVOLUTION
CELL FLOW SYSTEMS
GENE MUTATIONS
GENE REGULATION
GENETICS
MAMMARY GLANDS
NEOPLASMS
ONCOGENES
PATIENTS
PLOIDY
STATISTICS
THERAPY
TUMOR CELLS