Researchers detected circulating tumor cells (CTCs) in the portal venous blood of all patients with pancreaticobiliary cancer (PBC), but in the peripheral blood of only 22% of patients, according to a small single-center cohort study.
“We have shown that portal venous CTCs are far more common and higher in absolute numbers than peripheral blood CTCs. We also have shown the feasibility of obtaining portal venous CTCs noninvasively via endoscopic ultrasound,” Dr. Daniel Catenacci, Dr. Christopher Chapman, and their associates from the University of Chicago Medicine wrote in the December issue of Gastroenterology. “Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue.”
Circulating tumor cells have shown promise in the minimally invasive assessment of solid tumors, but the peripheral bloodstream contains only about one CTC for every 1 billion blood cells, limiting the potential sensitivity of testing. The researchers therefore used EUS guidance to transhepatically collect portal venous blood from 18 patients with PBCs. They quantified CTCs in both their portal venous and peripheral blood by using CellSearch, a commercially available test that uses magnetic beads labeled with antibodies against epithelial cell adhesion molecules. They only counted epithelial-derived cells as CTCs if they were morphologically compatible with tumor cells, CD45-negative, and positive for cytokeratins 8, 18, or 19 and 40,6-diamidino-2-phenylindole (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.08.050]).
Patients suffered no adverse affects from portal vein sampling, the researchers reported. They detected CTCs in the portal venous blood of all 18 patients, but in the peripheral blood of only four (22%) patients. Average CTC concentrations also were significantly higher in portal venous blood (118.4 ± 36.8 CTCs per 7.5 mL) compared with peripheral blood (0.8 ± 0.4 CTCs per 7.5 mL; P less than .01).
Among nine patients with nonmetastatic, resectable, or borderline-resectable PBC, portal vein CTCs averaged 83.2 per 7.5 mL (median, 62.0), the researchers reported. Whole-genome amplification and KRAS codon sequencing in one patient also showed that CTCs had the same mutations and similar levels of P16, SMAD4, and P53 proteins as tumor cells from a metastatic lymph node.
In addition, magnetic cell sorting identified CTC clusters, which other studies have implicated in the metastatic seeding of distant organs, the researchers said. Indeed, CTCs are now known to include “a heterogeneous population of cells, including apoptotic cells, cells undergoing epithelial-to-mesenchymal transition with loss of epithelial markers, epithelial cells, and cell clusters,” they noted. This heterogeneity might make CTCs useful for studying the pathogenesis and progression of PBCs, as well as for assessing the individual chances of recurrence or metastasis, they added. “Future prospective studies will define the role of portal vein CTCs or predictive biomarkers in the perioperative setting,” the investigators concluded.
The work was funded by the Rolfe Pancreatic Cancer Foundation, officers of the Gerald O. Mann Charitable Foundation, the National Institutes of Health, the University of Chicago Comprehensive Cancer Center, the Cancer Research Foundation, the Alliance for Clinical Trials in Oncology Foundation, and the Live Like Katie Foundation. The researchers reported having no conflicts of interest.
Source: American Gastroenterological Association