Histopathologic analysis of chromosome aneuploidy in ductal carcinoma in situ.
Formalin-fixed, paraffin-embedded sections from 28 cases of ductal carcinoma in situ (DCIS; 12 with coexisting invasive neoplasm) were analyzed for numerical alterations of chromosomes 7, 8, 16, and 17 by performing fluorescence in situ hybridization (FISH) using centromeric (alpha-satellite) probes. Based on signal counts in 200 to 300 nuclei, each hybridization was classified as disomic (copy loss in <40%, copy gain in < 10%), monosomic (copy loss 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 lesions were characterized by complete lack of significant chromosome gain, but 29% showed partial (focal) monosomy. Grade III lesions, in contrast, showed partial or complete trisomy/polysomy in 88% of hybridizations versus monosomy in only 4%. Grade II DCIS exhibited a mixed pattern of chromosome aneuploidy: 38% hybridizations were disomic, 36% trisomic/polysomic, and 26% monosomic (8 of 10 hybridizations showing complete monosomy occurred in grade II lesions). Disomic hybridizations exhibiting rare cells (5% to 10%) with copy gain were more frequent in tumors with coexisting invasive neoplasm (5 of 17 v 2 of 33, P = .02). In morphologically heterogeneous lesions, higher-grade foci were characterized by chromosome copy gain relative to corresponding lower-grade areas in 17 of 22 (77%) hybridizations. These results show the presence of multiple (at least 3) distinct chromosome aneuploidy patterns in DCIS, in keeping with divergent mechanisms of genetic alteration. Degree of chromosomal instability, moreover, may correlate with progression of DCIS to invasive growth, implying that genetic instability is a parameter that impacts the likelihood of early breast carcinoma progression.
Visscher
D
D
Department of Pathology, Harper Hospital, Detroit, MI 48201, USA.
Jimenez
R E
RE
Grayson
M
M
Mendelin
J
J
Wallis
T
T
D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002885:Chromosomes, Human, Pair 16; D002886:Chromosomes, Human, Pair 17; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009006:Monosomy; D014314:Trisomy