PREFERRED GENETIC EVOLUTIONARY SEQUENCES IN HUMAN BREAST-CANCER - A CASE-STUDY

Multiparameter flow cytometry studies were performed on the cells of a n aggressive human breast cancer at the time of diagnosis and at relap se, The aneuploid cells that overexpressed large amounts of both HER-2 /neu and ras survived intensive chemotherapy and were responsible for tumor relapse, At relapse, these cells were shown to overexpress simul taneously at least five oncogenes: HER-2/neu, ras, EGF receptor, p53 a nd c-myc, A partial reconstruction of the genetic evolutionary sequenc e in this tumor indicated that HER-2/neu overexpression was an early s tep in the sequence. Subsequent HER-2/neu overexpression, EGF receptor overexpression and p53 protein overexpression were each associated wi th ras overexpression, The data suggest that ploidy and oncogene overe xpression cannot be used as independent clinical prognostic factors, T he ability to characterize tumors according to the degree of advanceme nt in the genetic evolutionary might serve as a basis for genetic stag ing for adjuvant therapy. (C) 1995 Wiley-Liss, Inc.