【摘 要】
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Background: Cells released from the primary tumor persisting and recirculating in the host can lead to the formation of distant metastases.It was claimed that such cells are detectable only in a minor
【机 构】
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Department for Experimental Haematology und Oncology Clinic for Internal Medicine ⅡFriedrich Schille
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Background: Cells released from the primary tumor persisting and recirculating in the host can lead to the formation of distant metastases.It was claimed that such cells are detectable only in a minor fraction of early-stage cancer patients but we can show that CETC are detectable and can be quantified in the peripheral blood of almost all cancer patients including early-stage solid malignancies.Methods: Using anticoagulated peripheral blood, red blood cell lysis as the only enrichment step, one centrifugation step, staining live cells with fluorochrome labelled anti-epithelial antigen as a search antibody, automated image analysis for detection of positive events and evaluation of exclusively surface located epithelial antigen on vital unfixed cells, CETC were detected in most patients with early stage cancer.Subsequently cells could be stained with antiALDH-antibody and in situ hybridized for HER2/neu amplification and quantified repeatedly during neo/adjuvant chemotherapy and during maintenance therapy with hormones or trastuzumab.ResuRs: We here report the results from 497 breast cancer patients analyzed more than three times during the course of disease, 248 during neoadjuvant/adjuvant chemotherapy, 249 during trastuzumab arid or hormone therapy.Different pattern of therapy response were obtained with rapidly responding CETC changes over several logs in response to chemotherapy and slow and long-lasting changes extending over several years in response to hormone therapy and trastuzumab.Stem cell like staining was seen in a minor fraction of cells (1%) in about 10% of patients.An increase in cell numbers and in the fraction of HER2/neu amplified cells was under all treatment conditions unequivocally significantly correlated to highly increased risk of relapse.Conclusion: CETC and subpopulation monitoring provides an invaluable tool for prompt gauging of systemic therapy in early stage solid tumors as a tool for therapy guidance and optimal personalized therapies to improve therapy results and spare unnecessary treatments.
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