A circulating epithelial cell type merging stem cell, EMT, and hypoxic stress markers in early and advanced breast cancer.

Abstract

10600 Background: MAINTRAC as developed by our coworkers from Jena finds more CETC. They found CETC in 90% of high risk patients. Circulating cells in epithelial mesenchymal transition (EMT+) should be detectable in early disease. Methods: 2 colours (7AAD, EP-FITC) detected living and dead cells. Cells in EMT (EP-FITC, Vim-PE) were analysed in paralell. Complex marker expression urged us to introduce a three colour technique. 1. EPCAM-FITC, Vimentin-PE and DAPI , marking living or dead cells in EMT. 2. EP-FITC, Vim-PE and CD44 PB for stemness. ACA9 (hypoxia) and PARP-1 expression (genotox) were used too. Results: In the 2 colour phase we examined CEC in 110 patients with early disease and 44 patients with metastasis. Cells were detectable in both disease situations in 50 and 60% of patients, in a control population only in few patients low numbers were found. In non cancer situations e.g liver disease high numbers of EMT+cells were found.The results of 3 colour analysis are shown in the table. No clear differences between the classical risk groups are found, other subgroups are too small yet to be considered. Conclusions: Our findings show that in both disease situations cells merging EMT, stemcells ( EP+,Vim+.CD44+) and other markers are detectable. This cell type however is found also in non cancer conditions.We hypothesize that hypoxia is the common driver. Metastasis gives different patterns. Highly aggressive cancers show often none or few cells. In less agressive disease high cell numbers are found. We need to characterize the "benign" EMT phenomenon, as it could mingle with "real" CTC. Definitely liver is the source of these benign cells. Multi colour analysis will reveal the differences. Nevertheless monitoring of this special cell type could give new insights in the metastatic process in early and late disease. [Table: see text]