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From Chronic Feed-Induced Intestinal Inflammation to Adenocarcinoma with Metastases in Salmonid Fish

¹ Section of Fish Diseases, National Veterinary Institute; ² Section of Anatomy and Pathology, Institute of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science; ³ Department of Pathology and Forensic Odontology, Institute of Clinical Dentistry, Faculty of Dentistry, University of Oslo, Blindern; ⁴ Laboratorium for Patologi AS, Oslo, Norway and ⁵ Fiskehelsa BA, Valsøyfjord, Norway

Requests for reprints: Ole B. Dale, Section of Fish Diseases, National Veterinary Institute, Box 750 Dep, 0033 Oslo, Norway. Phone: 47-23216138; Fax: 47-23216101; E-mail: ole.b.dale{at}vetinst.no.

Key Words: Adenocarcinoma • feed • inflammation • intestine • teleost

Neoplasms in fish normally show poor abilities for metastasis, and there are no reports on intestinal cancer with metastasis to other organs. In aquaculture production, carnivorous salmonids in Northern Europe receive commercial feeds with plant ingredients. Such contents have been shown to cause chronic intestinal inflammation. Inflammation provokes carcinogenesis in the human gut, and here, we report a similar pathologic progression in salmonids. Nine commercially farmed groups of Atlantic salmon and rainbow trout (n = 39,160) and one experimental positive group (n = 789) fed the same commercial feed and two negative control groups (n = 3009) were investigated for the occurrence of intestinal tumors and metastases. Exposure period, gender, and sexual maturation were registered. Autopsy revealed an overall intestinal tumor occurrence of 10.62%, of which liver metastasis varied from 0% to 11.35% between the groups. Intestinal cancer prevalence increased from 0.50% to 14.81% during 4 months of feeding in the experimental group. A significant gender effect was registered in the commercially farmed groups but not in the experimental group. Histologic examination showed adenocarcinomas evolving through progressive epithelial dysplasia associated with severe chronic inflammation. One intestinal tumor was registered in one individual in the negative control groups. This is the first report on feed-induced intestinal carcinogenesis and metastasizing adenocarcinomas in fish fed an approved commercial diet. The pathogenesis was associated with a certain commercial diet provoking the inflammation-dysplasia-carcinoma sequence. The histologic progression was analogous to that of human colorectal cancer associated with inflammatory bowel disease. [Cancer Res 2009;69(10):4355–62]