Histopathologic analysis of chromosome aneuploidy in ductal carcinoma in situ

Formalin-fixed, paraffin-embedded sections from 28 cases of ductal carcinom a in situ (DCIS; 12 with co-existing invasive neoplasm) were analyzed for n umerical alterations of chromosomes 7, 8, 16, and 17 by performing fluoresc ence in situ hybridization (FISH) using centromeric (alpha-satellite) probe s. Based on signal counts in 200 to 300 nuclei, each hybridization was clas sified as disomic (copy loss in <40%, copy gain in <10%), monosomic (copy l oss in at least 50% of nuclei, partial if 40% to 49%) or trisomic/polysomic (copy gain in at least 20% of nuclei, partial if 10% to 19%). Grade I lesi ons were characterized by complete lack of significant chromosome gain, but 29% showed partial (focal) monosomy. Grade III lesions, in contrast, showe d partial or complete trisomy/polysomy in 88% of hybridizations versus mono somy in only 4%. Grade II DCIS exhibited a mixed pattern of chromosome aneu ploidy: 38% hybridizations were disomic, 36% trisomic/polysomic, and 26% mo nosomic (8 of 10 hybridizations showing complete monosomy occurred in grade II. lesions). Disomic hybridizations exhibiting rare cells (5% to 10%) wit h copy gain were more frequent in tumors with coexisting invasive neoplasm (5 of 17 v 2 of 33, P = .02). In morphologically heterogeneous lesions, hig her-grade foci were characterized by chromosome copy gain relative to corre sponding lower-grade areas in 17 of 22 (77%) hybridizations. These results show the presence of multiple (at least 3) distinct chromosome aneuploidy p atterns in DCIS, in keeping with divergent mechanisms of genetic alteration . Degree of chromosomal instability, moreover, may correlate with progressi on of DCIS to invasive growth, implying that genetic instability is a param eter that impacts the likelihood of early breast carcinoma progression. Cop yright (C) 2000 by W.B. Saunders Company.