ANEUPLOIDY IN BREAST-CANCER - A FLUORESCENCE IN-SITU HYBRIDIZATION STUDY

Although ploidy is associated with the development and progression of most breast cancers, the value of flow cytometric ploidy as a clinical prognostic factor remains controversial, The technique of fluorescenc e in situ hybridization (FISH) can be used not only to determine overa ll ploidy, but also to assess the over-representation or under-represe ntation of specific chromosomes in interphase cells, This information may be of prognostic value, We studied 84 primary breast cancers and 2 0 metastatic tumors by FISH, using chromosome-specific fluorescent cen tromeric probes, Of these, 100 cases were also studied by DNA flow cyt ometry, The FISH studies were concordant with DNA flow cytometry with regard to distinguishing aneuploid from diploid tumors in 78% of cases , The FISH data suggested that aneuploidy arises by a process of chrom osome complement doubling with subsequent chromosome loss, In tumors t hat exhibited evidence of more than one round of chromosome complement doubling, the selective accumulation of multiple copies of specific c hromosomes or chromosome segments was common, Multiple copies of chrom osomes centromeres 1, 3, and 17 were accumulated selectively in the ce lls of individual tumors more frequently than chromosomes centromeres 7, 11, and 16, Multiple copies of chromosomes centromeres 10 and 20 we re selectively accumulated only rarely, if at all, Aneuploidy in breas t cancer can be divided into distinct stages using fluorescence in sit u hybridization techniques, The stages of aneuploidy provide potential landmarks in the genetic evolution of this disease with possible link s to chromosome-specific evolutionary changes. (C) 1995 Wiley-Liss, In c.