DETECTION AND CHARACTERIZATION OF CARCINOMA-CELLS IN THE BLOOD

A highly sensitive assay combining immunomagnetic enrichment with mult iparameter flow cytometric and immunocytochemical analysis has been de veloped to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blo od. Peripheral blood (10-20 mi) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls wa s examined by flow cytometry for the presence of circulating epithelia l cells defined as nucleic acid(+), CD45(-), and cytokeratin(+). Highl y significant differences in the number of circulating epithelial cell s were found between normal controls and patients with cancer includin g 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytosp in preparations were made after immunomagnetic enrichment and were ana lyzed. Epithelial cells from patients with breast cancer generally sta ined with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast , no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consiste nt with that of neoplastic cells. Of 8 patients with breast cancer fol lowed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemot herapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.