Clone heterogeneity in diploid and aneuploid breast carcinomas as detectedby FISH

We investigated the relationship between DNA ploidy and alterations in chro mosomes 1, 8, 12, 16, 17, and 18 in 63 breast carcinoma samples by static c ytofluorometry and fluorescence in situ hybridization, Thirty specimens wer e diploid and 33 were aneuploid, In aneuploid samples, the DNA index value ranged from 1.3 to 3.1, with a main peak near tetraploid values. Diploid cl ones were present in 21 of 33 aneuploid specimens. Fluorescence in situ hyb ridization analysis showed a heterogeneous degree of alterations in diploid specimens: one sample was normal, 16 samples had one to three chromosome a lterations involving mostly chromosomes 1, 16, and 17, and 13 samples an ev en higher degree of alterations. The 33 aneuploid specimens showed a very h igh number of signals (four, five, or more). All the investigated chromosom es were affected in 23 of 33 specimens. Alterations in chromosomes 1 and 17 were detected to a similar percentage in diploid and aneuploid samples, wh ereas chromosome 16 monosomy was more frequent in diploid samples. Overrepr esentation of chromosomes 8, 12, 16, and 18 was significantly higher in ane uploid than in diploid samples, Based on these results, we suggest that dip loid and aneuploid breast carcinomas are genetically related. Chromosome 1 and 17 alterations and chromosome 16 monosomy are early changes. Allelic an d chromosomal accumulations occur during progression of breast carcinoma by different mechanisms. The high clone heterogeneity found in 17 of 33 aneup loid samples could not be completely explained by endoreduplication and led to the suggestion that chromosomal instability concurs with aneuploidy dev elopment. This different evolutionary pathway might be clinically relevant because clone heterogeneity might cause metastasis development and resistan ce to therapy. Cytometry (Comm, Clin, Cytometry) 46:50-56, 2001. (C) 2001 W iley-Liss, Inc.