We have developed a highly sensitive test for detecting, enumerating and characterizing epithelial cells in the blood. The test can detect one such cell in 2 x 108 leukocytes. The cells can be obtained viable or fixed. The method allows characterization of the cells for their malignant nature, genetic alterations, organ of origin and aggressiveness. We have used the method to study the blood of 34 patients with breast cancer, 7 with prostate cancer and 23 controls (normal or non-neoplastic disease). Tumor cells were found in the blood of virtually all the cancer patients, including those that had a tumor clinically confined to the primary site. There was no overlap in the number of blood epithelial cells in the controls vs 21 of 23 cancer patients with clinically organ confined tumor. The latter have cells with the morphology of tumor cells and those with breast cancer, express Mucin-1, cytokeratin, 8, 18, and frequently Her-2 and steroid receptors. We plan to optimize the assay including confirming the cut-off value for distinguishing blood from controls vs patients with cancer, more assays to determine the breast origin of the tumor cells, analysis of DNA alterations by multi-color FISH (MCF), the presence of mutations in oncogenes, cytology and characterization of surface antigens associated with replication and aggressiveness. Our hypothesis is that the assay will detect carcinomas at a very early stage and can aid prognostication. Thus, 1) Can circulating cancer cells be detected in high risk individuals before detection of the primary tumor? 2) Can the test be used to monitor therapy? 3) Can the test predict whether metastatic disease will develop? We also attempt to do short-term culture of the tumor cells from individual patients to study their reactivity to conventional and novel therapeutic agents.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Pathology B Study Section (PTHB)
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Lively, Tracy (LUGO)
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University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
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Page, Karen; Uhr, Jonathan W (2005) Mathematical models of cancer dormancy. Leuk Lymphoma 46:313-27
Fehm, Tanja; Sagalowsky, Arthur; Clifford, Edward et al. (2002) Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res 8:2073-84
Hayes, D F; Walker, T M; Singh, B et al. (2002) Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int J Oncol 21:1111-7
Fehm, Tanja; Morrison, Larry; Saboorian, H et al. (2002) Patterns of aneusomy for three chromosomes in individual cells from breast cancer tumors. Breast Cancer Res Treat 75:227-39