Immunohistochemical characterization of pancreatic tumors induced by dimethylbenzanthracene in rats

Dimethylbenzanthracene (DMBA) induces pancreatic adenocarcinomas in rats 9 months after carcinogen exposure, with precursor lesions (tubular complexes ) developing 1 month after initiation of treatment. Because previous studie s have suggested an acinar cell of origin for these tumors, we investigated the expression pattern of ductal, acinar, and islet cell markers in these cancers to gain insight into their phenotype and cell of origin. Pancreatic neoplasms were induced in rats by implantation of DMBA into the head of th e pancreas. Lesions studied included 10 early tubular complexes (DMBA for 2 weeks), 8 tubular complexes (DMBA for 1 month), and 10 adenocarcinomas (DM BA for 9 months). Normal rat pancreas served as a control, For comparison, 5 human ductal adenocarcinomas were also evaluated. immunohistochemistry wi th ductal (keratin, cytokeratin 19, cytokeratin 20), acinar (chymotrypsin), and islet (chromogranin A) cell markers was performed to analyze the tissu es. Rat tubular complexes and adenocarcinomas revealed strong expression of keratin, cytokeratin 19, and cytokeratin 20 in the cytoplasm of all neopla stic cells, absence of chymotrypsin, and rare immunoreactivity to chromogra nin A. Human adenocarcinomas showed strong expression of keratin and cytoke ratin 19 in all neoplastic cells, expression of cytokeratin 20 in 5-20% of cells, and absence of chymotrypsin and chromogranin A. Pancreatic adenocarc inomas induced by DMBA in rats express markers consistent with a ductal phe notype, as observed in human tumors, Ductal marker expression in early tumo r stages suggests a ductal cell of origin.