Journal
ONCOTARGET
Volume 8, Issue 49, Pages 86143-86156Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.21026
Keywords
pancreatic cancer; circulating tumor cells; KRAS; diagnostic leukapheresis; EMT
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Funding
- Bayer AG, Innovative Medicines Initiative Joint Undertaking (IMI JU)
- CANCER-ID [115749]
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It is now widely recognized that the isolation of circulating tumor cells based on cell surface markers might be hindered by variability in their protein expression. Especially in pancreatic cancer, isolation based only on EpCAM expression has produced very diverse results. Methods that are independent of surface markers and therefore independent of phenotypical changes in the circulating cells might increase CTC recovery also in pancreatic cancer. We compared an EpCAM-dependent (IsoFlux) and a size-dependent (automated Siemens filtration device) isolation method for the enrichment of pancreatic cancer CTCs. The recovery rate of the filtration based approach is dramatically superior to the EpCAM-dependent approach especially for cells with low EpCAM-expression (filtration: 52%, EpCAM-dependent: 1%). As storage and shipment of clinical samples is important for centralized analyses, we also evaluated the use of frozen diagnostic leukapheresis (DLA) as source for isolating CTCs and subsequent genetic analysis such as KRAS mutation detection analysis. Using frozen DLA samples of pancreatic cancer patients we detected CTCs in 42% of the samples by automated filtration.
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