AUTOMATED MICROSCOPY FOR RARE CANCER CELL DETECTION

Several studies demonstrated that the presence of occult micrometastases in bone marrow or peripheral blood (one cancer cell in one million "normal" cells) is predictive of a poor clinical outcome in patients with solid malignancies. Consequently, the ability to detect disseminated tumor cells at diagnosis and during therapy is essential for the optimal care of the oncology patient. Microscopical analysis based on immunocytochemistry using anti- cytokeratin antibodies is currently regarded as benchmark method for micrometastases detection. However, analysis cell numbers of 107 to 108 for the presence of cancer cells as a laborious task. In this project we will develop a fully automated Rare Event Localizer (REL) that can analyze 107 cells for the presence of cancer cells in less than 30 minutes. The core of the REL is a high-gain CCD camera, that covers large microscopic fields, and thus the need for time consuming scanning is eliminated. Our fluorescence based system will allow the detection of multiple markers at a single cell level. We will validate the performance of the REL by analyzing normal blood samples, seeded with cancer cells, and cancer patients' samples. We will also develop protocols for multiple marker analysis in breast, lung and prostate cancer.