HIGH PREVALENCE OF COLORECTAL-CANCER IN HLA-B27 TRANSGENIC F344 RATS WITH CHRONIC INFLAMMATORY BOWEL-DISEASE

Background/Aims: Transgenic rats expressing the human major histocompa tibility class I molecule HLA-B27 develop a spontaneous multisystem di sease that includes a chronic colitis resembling ulcerative colitis, T he availability of this phenotype in B27 transgenic rats of 2 differen t inbred strains provided the opportunity to inquire whether colorecta l neoplasia, which occurs with increased frequency in humans with infl ammatory bowel disease (IBD), would develop in either or both rat gene tic backgrounds. Methods: Clinical and histologic evaluation of B27 tr ansgenic rats with chronic inflammatory bowel disease (IBD) on the F34 4 and LEW inbred backgrounds. Results: In B27 transgenic rats on an in bred F344 background, hyperplastic lesions evolved in the setting of c hronic colitis, with a high frequency of colorectal polyp formation an d frequent histologic progression from adenoma to adenocarcinoma, In c ontrast, no neoplasia occurred in B27 transgenic rats on an inbred LEW background, despite similar colitis. Conclusion: A high incidence of spontaneous colorectal neoplasia occurs in a line of B27 F344 rats tha t shares some features of both sporadic and inflammatory bowel disease -associated human colorectal cancer, This represents a novel example o f spontaneous colorectal neoplasia in rodents that is not based on ger mline modification of one or more already-identified cancer-related ge nes.