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Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11 222, Palmerston North, New Zealand (JSM, MMB), and Diagnostic Center for Population and Animal Health, Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University (MK)
Around 1.6% of sheep in New Zealand develop small-intestinal adenocarcinomas. These neoplasms typically develop widespread metastases. The common development of these neoplasms and their subsequent behavior suggests that sheep could be a useful animal model of human colonic cancer. However, for an animal model of human disease to be relevant, similar genetic mutations should be present. Genetic mutations within human colonic cancers frequently result in expression of cycloxygenase-2 (COX-2), loss of membranous expression of ß-catenin and E-cadherin, and accumulation of p53 protein within the neoplastic cells. Immunohistochemistry was used to investigate the presence of these 4 proteins within 26 ovine intestinal adenocarcinomas. Loss of membranous ß-catenin reactivity was observed in 14 of 26 ovine intestinal adenocarcinomas (54%). The loss of membranous ß-catenin reactivity was accompanied by cytoplasmic and nuclear reactivity in 2 neoplasms. Loss of E-cadherin was observed within 8 of 26 neoplasms (31%). Neoplastic cell expression of COX-2 was observed in 12 of 26 neoplasms (46%), whereas cells within 3 of 26 neoplasms (11%) contained visible p53 protein. In conclusion, all 4 proteins that commonly have altered expression in human colonic cancers were also altered in a proportion of the ovine intestinal adenocarcinomas. These results provide additional evidence that sheep could be useful for the study of human colonic cancer.
Key words: Animal model; ß-catenin; COX-2; colon cancer; E-cadherin; intestinal adenocarcinoma; p53 protein; sheep.
Request reprints from John S Munday, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11 222, Palmerston North, (New Zealand). E-mail: J.Munday{at}massey.ac.nz
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J. S. Munday, F. A. Frizelle, and M. R. Whitehead Mismatch Repair Protein Expression in Ovine Intestinal Adenocarcinomas Vet. Pathol., January 1, 2008; 45(1): 3 - 6. [Abstract] [Full Text] [PDF] |
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