[Pancreatic intraepithelial neoplasia in chronic pancreatitis]

Chronic pancreatitis causes destruction of the pancreatic gland which leads to tissue fibrosis and regenerative hyperplasia of the epithelium of pancreatic ducts and ductules. Morphological studies revealed distinct proliferative lesions in the pancreatic ducts and ductules adjacent to infiltrating adenocarcinomas of the pancreas. A stepwise progression from mild to severe dysplasia in these hyperplastic lesions has been reported. These lesions, called Pancreatic Intraepithelial Neoplasia (PanIN), harbour a number of well-characterised genetic alterations. Therefore, PanINs were defined as true clonal neoplastic lesions with minimal to moderate and severe cytological and architectural atypia. Almost all of the genetic alterations that have been identified in pancreatic adenocarcinomas have also been identified in PanIN lesions. The prevalence of genetic changes increases as the degree of cytological atypia and histological dysplasia in the PanIN lesions increases. However, some genetic abnormalities have also been found in chronic pancreatitis and normal pancreas, e. g. K-ras mutations. However, due to intratumorous heterogeneity of the genetic changes, further studies are necessary to search for more specific and homogeneous expressed molecular markers. A better understanding of the molecular genetic changes occurring during neoplastic progression in the pancreas will form the basis for future strategies of early tumour detection and improved therapy.