Pathology of mouse models of intestinal cancer: Consensus report and recommendations

The marked diversity in the phenotype of intestinal neoplasia in murine models offers opportunities to model many characteristics of human CRC, including tumor progression, metastasis, gross morphology, and histology. However, the lack of a consistent model of metastasis is of particular concern in developing mouse models of human CRC. AOM-treated mice consistently develop metastasis, but the absence of control by known genetic mutations under carcinogen treatment makes this model system less desirable. The Smad3-/-, PI(3)Kγ-/-,90 and Apc1638N/+ mutants are the only mouse models reported to develop colonic adenocarcinomas that metastasize to the lymph nodes and liver, which are common metastatic sites of human CRCs. However, there has been difficulty reproducing this observation in similar strains from different laboratories. Neoplastic lesions in mice with specific genetic alterations often do not parallel the phenotype of human cancer. Lastly, the role of intestinal pathogens and their contribution to the inflammatory response and tumor initiation is generally underappreciated. Despite these limitations, mouse models are invaluable in approximating the pathogenesis of human intestinal cancer and thus provide an in vivo platform for identifying therapeutic targets and developing new strategies for prevention and treatment.