Detection of circulating tumor cells and micrometastases in stage II, III,and IV breast cancer patients utilizing cytology and immunocytochemistry

Evaluation for circulating tumor cells and bone marrow micrometastases has generated considerable interest due to a potential association with disease recurrrence and poor prognosis. In this study, we examined bone marrow and apheresis samples from Stage II, III, and IV patients (n 120) enrolled in various clinical breast cancer trials at the National Institutes of Health/ National Cancer Institute. For each patient sample, two Diff-Quik-stained c ytospins were reviewed for morphology, and approximately 1 10(6) cells were analyzed for the expression of cytokeratins using an avidin-biotin immunop eroxidase method. Keratin-positive malignant cells appearing as single cell s or in small clusters were detected in bone marrow samples from Stage IV p atients only (9/68, 13%) and detected in apheresis samples from both Stage III and IV patients (13/245, 5%). These findings indicate that the combinat ion of cytomorphology with immunocytochemistry can be utilized Sor the inve stigation of circulating tumor cells and bone marrow micrometastases, and t hat positive results appear to correlate with high tumor stage/burden. Diag n. Cytopathol. 2000; 22:323-328. Published 2000 Wiley-Liss, Inc.