The occurrence of prion protein in surgically resected pancreatic adenocarcinoma

Background and Objectives: A number of markers are tested to diagnose, predict and follow up the course of pancreatic ductal adenocarcinomas (PDAC). The smoldering course of the disease and its severe propensity to spread along unconventional pathways call for establishing early markers of PDAC. Moreover, disclosing specific molecules related to the growth and malignancy of PDAC may foster the pathway to better understand the biology of the disease. Prion protein (PrP) is a cell surface glycoprotein quite ubiquitously expressed in various cell types. Recent evidence obtained in a variety of malignancy within the GI tract indicates that the expression of PrP is related with tumor stemness, invasiveness and resistance to chemotherapy. Similarly, very recent data obtained from glioblastoma cells indicate that PrP is markedly expressed within the tumor-initiating cells, which are responsible for development, dissemination and relapse of the disease. Some recent manuscripts investigated the molecular mechanisms which links the expression and abundance of PrP within tumor cells and the activation of genes involved in cell proliferation and migration. However, no study so far investigated in vivo the occurrence of PrP within PDAC. In vitro evidence in cell cultures showed the occurrence of PrP in PDAC cells while PrP was absent in normal pancreatic cell lines. The aim of this study was to evaluate the presence of PrP in PDAC tissue as possible marker of specific biological behavior. Materials and Methods: Between July 2018 and March 2019, samples from tumors of 14 patients underwent pancreatic resection for PDAC were collected. Immunohistochemistry and western blotting of PDAC tissues were compared with non PDAC tissues such as those of non-affected neighboring tissue of the same patient, and of pancreatic tissue from patients affected by pancreatic disorders other than PDAC. Results: All patients were affected by moderately differentiated PDAC. Perineural invasion was reported in 10/14 cases of PDAC (71.4%). Both immunohistochemistry and western blotting revealed a remarkable difference in PrP presence between PDAC tissues and non-affected pancreatic areas. Conclusion: The presence of PrP in PDAC tissue might be a marker that might contribute to explain the biology of PDAC disease, in particular its neurotropism. In order to document the sub-cellular compartmentalization of PrP, studies are in progress to detect the specific presence of PrP within specific cell compartments and cell types