Evaluation of chromosome aneuploidy in tissue sections of preinvasive breast carcinomas using interphase cytogenetics

Little is known about cellular level genetic alterations in preinvasive breast lesions, particularly lobular carcinoma in situ.

We employed fluorescence in situ hybridization (FISH) using pericentromeric (alpha satellite) probes to assess numerical alterations of chromosomes 1, 7, 8, 16, 17, and X in deparaffinized archival tissue sections of 9 lobular carcinomas in situ (LCIS), 10 ductal carcinomas in situ (DCIS), and a spectrum of proliferative lesions (including 3 ductal hyperplasias, 1 adenosis, 1 radial scar, and 2 atypical hyperplasias). Three of the LCIS lesions and five of the DCIS lesions were from patients who had a concurrent invasive neoplasm as a component of the tumor.

None of the proliferative lesions exhibited detectable chromosome gains, and only 1 showed evidence of signal loss consistent with monosomy (chromosome 7 in the adenosis lesion). Six LCIS patients (67%) displayed evidence of monosomy, with involvement of chromosome 17 in 6 of 6 patients, chromosome 8 in 2 of 6 patients, and chromosome 7 in 2 of 6 patients. Two LCIS patients, each of whom had a concurrent invasive neoplasm, exhibited signal gains consistent with trisomy for chromosomes 1 and 8 (1 patient each). Chromosome aneuploidies were observed in 7 of 10 (70%) DCIS patients, including 2 of 5 patients (40%) without concurrent invasive neoplasm and 5 of 5 patients (100%) with concurrent invasive neoplasm. The pattern of numerical chromosome alteration in DCIS included two patients with losses only, 2 patients with gains only, and 3 patients with both gains and losses (i.e., involving different chromosomes). Chromosome 17 aneuploidy was observed in all DCIS and all LCIS patients who exhibited abnormalities; however, DCIS patients showed more frequent aneuploidies for chromosomes X and 16 (0 LCIS patients vs. 4 DCIS patients with each).

Distinctive pathologic subsets of preinvasive breast neoplasia have divergent patterns of genetic instability. Foci of residual in situ neoplasia that accompany invasive disease may have a greater degree of genetic instability than neoplasms that lack progression to invasive phenotype.