Abstract P1-07-16: Liver derived epithelial cells as source of false positive circulating tumor cells in early breast cancer

Abstract

Abstract The MAINTRAC technique as introduced by our coworkers from Jena (RBC lysis, fluorometric detection and analysis on Olympius ScanR) detects more circulating epithelial cells than techniques using enrichment. Also cells with a low EPCAM expression are detected and not only the typical cells with bright expression found after immunomagnetic enrichment. The relative cheapness and reproducibility allows frequent monitoring during and after therapy Using 3 colour detection (EPCAMfitc, DAPI, Vimentin PE) living and dead circulating epithelial cells in EMT, or cells in EMT with stemcell markers (EPCAMfitc, Vimentin-PE, CD44PacBlue) can be detected. In early breast cancer (n = 135) cells can be found in 60% of patients and in 40% higher cell counts (>100 ml are detectable. A control population(n = 100) showed low numbers in 98% (e.g (<100 CECin 1 ml blood). Expression of the mesenchymal marker (vimentin) ranges between 10 and 40% with different expression. CD44 shows also a wide range of expression. Two main cell types can be distinguished: type 1 shows generalized but weaker expression patterns and a second type with very bright dotted expression. The clinical relevance of these subsets is not known and their behavior under therapy has not been analysed in depth yet. In advanced breast cancers high cell counts were detectable in most patients with a less agressive disease course. In the rapidly progressing unfavorable subtypes (TN and Her2+. HRneg) less or none cells were found. During crossvalidation in non cancer patients we found high cell numbers in several forms of liver affections (n = 108). The expression patterns of markers on these cells were not differing from those in cancer patients. So this same cell type merging EMT, stemcell an hypoxic stress markers is detectable in advanced and early breast cancer (n = 40) and in benign disease. These cells disappear or decrease after response to chemo or anti-hormonal therapy in cancer or antioxidant therapy in NAFLD. We believe that the evasion of these cells is driven by the same force in cancer as in non cancer conditions. We suggest that this are the wellknown hypoxic and hyperacidic conditions causing epithelial mesenchymal transition. Cancer cell hijack this functions occurring normally under these conditions to survive and to facilitate evasion. More comprehensive analysis (four colour analysis on the AMNIS Flowsight) is needed and should show differences in expression patterns of liver derived epithelial cells (LDEC) and real tumor derived epithelial cells (TDEC). Further clarification of these phenomena should give new insights of the biological events in early disease and the possibilities and reliability of “fluid biopsy”. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-16.