Parviz M Pour, Geoffrey Talmon
Background According to numerous studies in the hamster pancreatic cancer model, islet cells are the most vulnerable to a carcinogen’s insult and the induction of islet cell proliferation enhances the neoplastic process, however, the prevention of islet cell neogenesis inhibits it. In humans, however, discrepancies exist on the nature of the cancer progenitor cells. The recent discovery of islet cell expansion by GLP-1 analogs in type 2 diabetics offered a unique opportunity for comparative studies. Materials and Methods The pancreatic tissue of a type 2 diabetic who was treated with Victoza and Byetta for 25 months and died about a year later from pancreatic cancer, was evaluated histologically and by immunohistochemistry. Results Differences were found relative to the patterns of the distribution of islets in the tissue derived from the ventral and dorsal anlage of the pancreas. In the glucagon-rich and PP-poor dorsal pancreas, most islets were well circumscribed and atrophic but many contained intrainsular ductules that were malignant in one case. In the PP-rich, glucagonpoor ventral pancreas, the islets were ill-defined, varied in size and shape, were much larger than in the control tissue, and in one area presented malignant growth. In the PP cell dominated area, islet cell transformation to normal, atypical and malignant ductular structures in various stages of differentiation were found, and remarkably in multiple sites. Conclusion This is the first report demonstrating that: 1) as in the hamster pancreatic cancer model, human islets also appear to present a source of pancreatic ductal neoplasms; and 2) the alterations seem to be related to the effects of GLP-1 analogs.
