ANALYTICAL APPROACHES RELATING GENETIC EVOLUTIONARY PATHWAYS TO PROGNOSTIC FACTORS

Human solid tumors accumulate multiple genetic abnormalities as they p rogress to advanced stages. Multiparameter now 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 now cytometry studies of pr imary breast cancers from 92 patients. These laboratory findings were correlated with established clinical prognostic factors for each patie nt at the time of diagnosis, using a stepwise multiple analysis of var iance (MANOVA). The stepwise MANOVA successively splits a group of pat ients into two mutually exclusive dissimilar groups, selecting the cli nical 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 posi tive nodes at the time of diagnosis, We show that ploidy, HER-2/neu pr otein content, and ras protein content, as measured by multiple parame ter now cytometry, are correlated with nodal status and other known cl inical prognostic factors, The cell-by-cell multiparameter data sugges t that for some individual tumors there are multiple genetic evolution ary pathways, Multiple genetic evolutionary pathways are also suggeste d by the MANOVA analysis. Focusing on the identification and analysis of genetic evolutionary pathways within individual tumors and across p atients appears to offer a promising approach for defining the prognos is of early cancers. (C) 1995 Wiley-Liss, Inc.