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

Tumor Biology
Session Type and Session Title: 
General Poster Session, Tumor Biology
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 10600)
Leo Habets, Wolfgang Koerber, Bettina Frenken, Ilham El Ghali, Mahmoud Danaei, Manfred Kusche, Uwe Peisker, Torsten Kroll, Katharina Pachmann; Metares e.V, Aachen, Germany; Metares e.V, Aachen, AL, Germany; Brustzentrum Aachen Kreis Heinsberg, Aachen, Germany; Brustzentrum Aachen Kreis Heinsberg, Erkelenz, Germany; University of Jena, Jena, Germany

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Abstract Disclosures


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.
Cell type EMT living EMT total EMT+CD44
CEC per ml <250 >250 <250 >250 <250 >250
ALL 56 44 21 79 25 75 n=60
N0 80 20 41 59 57 43 n=36
N+ 64 26 51 49 34 66 n=24
Lum A 48 52 20 80 34 66 n=30
Lum B 48 52 31 69 23 77 n=29
Advanced 39 61 27 73 37 63 n=40
Controls 98 2 91 9 81 19 n=112
"Liver " 10 90 22 78 n=84