Heterogeneous expression of tumor-associated genes in disseminated breast cancer cells.

BACKGROUND Gene expression profiles were determined to demonstrate heterogeneity of viable disseminated tumor cells (DTC) in the blood of breast cancer patients. PATIENTS AND METHODS All patients (n = 48) suffered from metastatic disease (M1) and were treated with chemotherapy and/or Herceptin, respectively. Blood samples were analyzed by a DTC detection assay consisting of immunomagnetic tumor cell selection combined with expression profiling of the tumor-associated transcripts GA733-2, MUC-1, HER-2 and Claudin-7. In addition, the correlation of HER-2 expression in DTC with histopathologically determined HER-2 status in distant metastases and primary tumors in selected cases was investigated. RESULTS DTC were detected in 69% (p < 0.0001) of breast cancer patients. The expression profiles were shown to be heterogeneous within different patients and even within the follow-up period of patients, reflecting the expected heterogeneity of DTC. Furthermore, preliminary results showed a correlation between HER-2 gene expression in DTC and HER-2 overexpression in tumor tissue of distant metastases. CONCLUSION The results suggest a clinical value of the DTC detection assay with respect to a more precise characterization of individual cancer disease and selection for therapy. More emphasis should be placed on HER-2 expression in DTC as a possible precursor of distant metastases.