Cancer cells have long been believed to acquire metastatic potential after large primary tumors are established. However, many patients undergoing pancreatectomy for chronic pancreatitis are found to have disseminated pancreatic ductal adenocarcinomas (PDAC), even though only precancerous pancreatic intraepithelial neoplasias were detected by histologic analysis.
Furthermore, among patients with small primary tumors (<2 cm) with no evidence of metastatic disease, only 18% survive for 5 years after pancreatectomy—most patients still develop recurrent, metastatic disease. Metastatic cancer cells therefore appear to start spreading before large primary tumors develop.
Andrew Rhim et al. investigated whether pancreas-derived epithelial cells might be detected in blood samples from patients with evidence of only precancerous lesions of the pancreas—with no detectable invasive carcinomas.
They collected and analyzed blood samples from patients with intraductal papillary mucinous neoplasm (IPMNs) or mucinous cystic neoplasms but no evidence for tumors or metastases, along with patients with cytology-confirmed PDAC and no cysts or cancer (positive and negative controls, respectively).
Using microfluidic geometrically enhanced differential immunocapture, they found more than 3 circulating pancreas epithelial cells/mL in blood samples from 7 of 21 patients (33%) with cystic lesions and no diagnosis of cancer (Sendai-criteria negative), 8 of 11 patients (73%) with PDAC, and in 0 of 19 patients without cysts or cancer (controls).
Therefore, pancreas epithelial cells from patients with cystic lesions or cancer enter the bloodstream.
Studies are underway to analyze the genetic features of circulating pancreatic endothelial cells from patients with cystic lesions, to see if the cells already have somatic mutations associated with PDAC. It is not clear whether patients with these cells in their circulation all develop tumors.
If the cells are associated with subsequent tumor formation, their detection in blood samples could be a marker of PDAC risk. Rhim et al. are planning studies to follow patients with cysts to determine if number or genomic features of circulating pancreatic cells can predict the development of PDAC.