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.
BACKGROUND: Gene expression profiles were determined to demonstrate heterogeneity of viable disseminated tumor cells (DTC) in the blood of breast cancerpatients. 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 cancerpatients. 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.
Authors: I Van der Auwera; D Peeters; I H Benoy; H J Elst; S J Van Laere; A Prové; H Maes; P Huget; P van Dam; P B Vermeulen; L Y Dirix Journal: Br J Cancer Date: 2009-12-01 Impact factor: 7.640