Colossal crypts bordering colon adenomas in Apc(Min) mice express full-length Apc.

Enlarged but nondysplastic crypts are frequently observed at the margins of colon tumors, forming what has been called a transitional epithelium. It is now thought that this is a reactive state and not a preneoplastic condition as previously suggested. We have used the mouse familial adenomatous polyposis model, ApcMin, to study these abnormal adenoma-associated crypts. We report that these nondysplastic crypts are enormous (as much as 10 times normal length) and branch more frequently than normal crypts. They express wild-type Apc protein and display the wild-type Apc allele. We conclude that the colossal crypts at adenoma margins have normal Apc gene function, consistent with the suggestion that their phenotype is a reactive state. The cause remains an open question, but the dramatic epithelial response hints at the presence of potent epithelial trophic factors in the vicinity of colon tumors.