Induction of duodenal mucosal tumors of intestinal epithelial cell origin showing frequent nuclear β-catenin accumulation similar to the concurrently induced colorectal tumors in rats after treatment with azoxymethane

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2015-05, Vol.67 (5-6), p.349-353
• Main Authors: Kikuchihara, Yoh, Onda, Nobuhiko, Kimura, Masayuki, Kangawa, Yumi, Mizukami, Sayaka, Yoshida, Toshinori, Shibutani, Makoto
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemically induced; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Azoxymethane; Azoxymethane - toxicity; beta Catenin - metabolism; Carcinogenesis - chemically induced; Carcinogens - toxicity; Colorectal Neoplasms - chemically induced; Colorectal Neoplasms - pathology; Cytokeratin; Duodenal Neoplasms - chemically induced; Duodenal Neoplasms - metabolism; Duodenal Neoplasms - pathology; Duodenal tumors; Duodenum - drug effects; Duodenum - metabolism; Duodenum - pathology; Histogenesis; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Male; Mucin; Rat; Rats; Rats, Inbred F344
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2015.03.002

Azoxymethane (AOM) is a potent carcinogen used for induction of colon tumors in rats and mice. It is also known that AOM treatment induces small bowel tumors in addition to colorectal tumors in rats. The present study examined the histogenesis of AOM-induced rat duodenal tumors in comparison with concurrently induced colorectal tumors by histochemical and immunohistochemical approaches. Duodenal and colorectal tumors were positive for both periodic acid-Schiff reaction and Alcian blue staining. Immunohistochemically, duodenal tumors were positive for intestinal epithelial markers such as cytokeratin (CK) 20 (100%) and mucin (MUC) 2 (91.7%) but negative for pancreaticobiliary markers such as CK7 (100%) and MUC1 (100%). All colorectal tumors were also negative for CK7 and MUC1 but positive for CK20. Eighty percent of colorectal tumors were positive for MUC2. In addition, nuclear accumulation of β-catenin was found in duodenal tumors (70.8%), which was similar to colorectal tumors (90.0%). These results indicate that duodenal tumors induced by AOM treatment of rats were derived from intestinal epithelium. Similar to colorectal tumors, nuclear accumulation of β-catenin indicates activation of Wnt signaling as a driving force for tumor progression in AOM-induced duodenal tumors.