Nonisotopic fluorescence in situ hybridization by using alpha satellite centromeric probes was performed on intact tissue sections of 12 breast carcinomas to compare the pattern of aneuploidy for chromosomes 7, 8, 16, and 17 between foci of residual in situ carcinoma (DCIS) and a representative area of coexisting invasive neoplasm. Most hybridization pairs (58%) showed a gain in chromosomal copy number between the in situ and corresponding invasive area, whereas 29% showed no apparent change and 13% showed loss in copy number. Hybridizations from areas of invasive carcinoma, thus, were more frequently characterized by tumor cells with trisomy/polysomy (78%) than neoplastic cells from residual DCIS (50%) and less frequently characterized by cells with monosomy (10% versus 16%, p = 0.01). Even when DCIS cells exhibited chromosome trisomy, 65% of hybridizations demonstrated a significantly greater proportion of trisomic cells in the corresponding invasive population. The hybridization pairs (n = 7) initially showing apparent loss in chromosome copy number from in situ to invasive growth were all from two cases that demonstrated morphologic heterogeneity. Enumeration of cells from histologically distinct areas of these cases revealed different patterns of aneusomy, in keeping with karyotypic diversity. However, comparison of histologically similar areas of DCIS and invasive neoplasm demonstrated a pattern of chromosome copy gain with invasive growth, similar to morphologically homogeneous tumors. We conclude that invading cells in breast carcinomas differ from residual in situ populations with respect to degree of chromosome aneuploidy and that tumor progression from preinvasive to an invasive phenotype in human breast carcinoma is characterized by a significant increase in the degree of genetic instability. The observed pattern of chromosome copy number gain, moreover, is consistent with a common cellular level genetic mechanism underlying early breast tumor progression.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Apr 1 1999|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Molecular Biology
- Cell Biology