Interphase cytogenetics reveals a high incidence of aneuploidy and intra-tumour heterogeneity in breast cancer.

The occurrence of aberrations involving chromosomes 11 and 17 in malignant tissues of breast cancer patients has not yet been studied systematically. Using fluorescence in situ hybridisation (FISH) with centromere-specific probes, we determined chromosome 11 and 17 status in interphase nuclei from primary and/or metastatic breast cancer cells. In all cancerous specimens obtained from 30 patients, FISH identified cells with clonal chromosomal abnormalities, with aneuploidy rates ranging from 6% to 92% (median 59%). There was a gain of centromeric signals for chromosome 11, most likely corresponding to hyperploidy; aberrations of chromosome 17 in specimens from 26 patients (87%) were hyperploid as well; however, four cases (13%) showed loss of chromosome 17 centromeres. All specimens contained heterogeneous aneuploid cell populations with excessive gain of signals in some cases. The pattern of aneuploidy did not appear to correlate with tumour grade/stage and was comparable in primary tumours and corresponding metastatic axillary lymph nodes, indicative of genetic instability early in tumour development. Screening with a panel of FISH probes may lead to enhanced sensitivity and specificity in detecting malignant cells, as demonstrated in this study with effusions which could not be conclusively interpreted as being malignant by cytological criteria.