Transcriptomic signature and microenvironment of early neoplastic lesions in pancreata of brain dead donors

The adult healthy human pancreas has been poorly studied given lack of indication to obtain health tissue from the pancrease in the absence of disease and rapid postmortem degradation. Researchers at the University of Michigan (Ann Arbor) obtained pancreata from brain dead donors thus avoiding any warm ischemia time. The donors were diverse in age (20 to 70 years at time of death) and race and had no known pancreas disease. Histopathologic analyis of the samples revealed pancreatic intraepithelial neoplasm (PanIN) lesions in most individuals (60%). Using a combination of immunohistochemistry, RNA sequencing, and transcriptomics, the study provided the first ever characterization of the microenvironment of the adult human pancreas and of sporadic PanIN lesions. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis.