Several molecular and immunohistochemical assays have been established to detect epithelial cells in blood of breast cancer patients. The malignancy of these cells, however, has not been proven. Aneuploidy is an early feature of primary breast cancer. The aim of this study was to determine (1) are epithelial cells in the blood of breast cancer patients aneuploid and (2) does their pattern of aneuploidy match that of the primary tumor. Methods: Cytospins were prepared from 5 ml anticoagulated blood samples of breast cancer patients enriched for epithelial cells by positive immunomagnetic selection. Epithelial cells were detected by immunofluorescent staining using a pan-cytokeratin (CK)-antibody. Samples with morphologically intact CK-positive cells (n=15) were then hybridized with centromeric (CEP 1, 3, 7, 8, 11 or 17) and locus-specific (her-2 or c-myc) DNA-probes by dual or tricolor-FisH. If primary tissue was available (n=7), touch preparations were made and genotpyed with the same set of probes to compare the aneuploidy pattern. Results: The number of epithelial cells varied from 1-28 cells / cytospin (average: 6 cells). Nine patients had more than 1 CK-positive cell. Circulating epithelial cells displayed numerical aberrations for at least one of the DNA-probes in 12 of the 15 patients. The aberration pattern was homogenous in 5 of the 7 patients with more than 1 aneuploid CK-positive cell. From 5 patients with aneuploid blood epithelial cells, touch preparations from the corresponding primary tumor could be genotyped. The aneuploid pattern matched in 4 of the 5 patients. Conclusions: Our study indicates that most of the circulating epithelial cells of breast cancer patients are aneuploid. Comparison of the aneuploid pattern of circulating CK-positive cells and primary tumor provides proof of the malignancy of the epithelial cells in the blood of these patients.
|Original language||English (US)|
|Number of pages||1|
|Journal||Breast Cancer Research and Treatment|
|State||Published - Jan 1 2001|
ASJC Scopus subject areas
- Cancer Research