Analysis of chromosome aneuploidy in breast carcinoma progression by usingfluorescence in situ hybridization

Nonisotopic fluorescence in situ hybridization by using alpha satellite cen tromeric probes was performed on intact tissue sections of 12 breast carcin omas 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 g ain in chromosomal copy number between the in situ and corresponding invasi ve area, whereas 29% showed no apparent change and 13% showed loss in copy number. Hybridizations from areas of invasive carcinoma, thus, were more fr equently characterized by tumor cells with trisomy/polysomy (78%) than neop lastic cells from residual DCIS (50%) and less frequently characterized by cells with monosomy (10% versus 16%, p = 0.01). Even when DCIS cells exhibi ted chromosome trisomy, 65% of hybridizations demonstrated a significantly greater proportion of trisomic cells in the corresponding invasive populati on. The hybridization pairs (n = 7) initially showing apparent loss in chro mosome copy number from in situ to invasive growth were ail from two cases that demonstrated morphologic heterogeneity. Enumeration of cells from hist ologically distinct areas of these cases revealed different patterns of ane usomy, in keeping with karyotypic diversity. However, comparison of histolo gically similar areas of DCIS and invasive neoplasm demonstrated a pattern of chromosome copy gain with invasive growth, similar to morphologically ho mogeneous tumors. We conclude that invading cells in breast carcinomas diff er from residual in situ populations with respect to degree of chromosome a neuploidy and that tumor progression from preinvasive to an invasive phenot ype 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.