Molecular characterization of circulating tumour cells in patients with breast cancer.

The detection of minimal disease in blood of patients with cancer is hampered by a lack of sensitivity and accuracy of the currently available tests. The availability of the real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and the possibility to measure the expression of multiple genes simultaneously has initiated some change in this area. In previous research we showed a superior sensitivity of qRT-PCR for CK-19/MAM compared to immunocytochemistry for the detection of disseminated tumor cells (DTCs) in bone marrow and to the FDA approved CellSearch System (Veridex, Raritan, NJ) for the detection of circulating tumor cells (CTCs)in peripheral blood. Through the molecular characterization of CTCs in patients with metastatic breast cancer, this project aims to identify a set of markers that can be used to further enhance the sensitivity of the currently available qRT-PCR test. In addition, characterization of CTCs can improve our insight in the pathogenesis of cancer metastasis. By comparison of the gene expression profiles of blood samples enriched for CTCs and the residual CTC-depleted blood samples, a CTC-specific genome-wide gene expression profile will be generated. Crossvalidation of these discriminatory genes will be done on the primary tumor. Using discriminant analysis with theexpression profile of healthy volunteers, an optimization of the amount of markers and their expression level will be determined to achieve a zero misclassification of healthy volunteers (sensitivity 100%) and an as correct as possible classification of patients with breast cancer.

Keywords:ONCOLOGY, BREAST CANCER

Disciplines:Laboratory medicine, Morphological sciences, Oncology