Preston, S.; Wong, R.; Brittan, M.; Direkze, N.; Novelli, M.; Tomlinson, I.P.; Poulson, R.; Lee, C.; Goodlad, R.; Mandir, N.; Bodmer, W.; Wright, N.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA30
Academic Journal
Introduction: The adenoma-carcinoma sequence is well established. Understanding the molecular pathology of the adenoma is therefore important. There is great controversy within the field. The Vogelstein group champion the "top down" theory: colorectal adenomas arise and grow across the mucosal surface, and down into the crypts, whereas other studies, including our own, propose 'bottom up' spread. Methods: Serial sections of 40 small (< 3 mm) sporadic colorectal adenomas were stained with H&E, and for MIB-1 and β catenin. 11 early adenomas were Feulgen stained and microdissected. In addition, we examined the flat mucosa of 3 patients who had undergone colectomies for familial adenomatous polyposis (FAP) and also specimens from an XO/XY individual with FAP, the latter using in situ hybridisation for the Y chromosome. Results: In the earliest sporadic adenomas there were crypts entirely filled with adenomatous epithelium, which showed proliferative activity and nuclear Iocalisation of catenin. There was a sharp cut off beh,veen crypt epithelial cells showing nuclear β catenin and surface cells with no membrane staining. In slightly larger lesions, adenomatous spread from above was seen. Microdissected adenomas showed multiple fission events, with proliferation equally distributed throughout. In FAP tissue, numerous isolated monocryptal adenomas, which were clonal in origin, were seen. Examination of adenomas in the XO/XY individual showed no instances of XY or XO adenomatous epithelium growing down into crypts of the other genotype. Conclusions: Both sporadic and FAP adenomas start as a unicryptal adenomas, and grow initially by crypt fission—a "bottom up" pattern. Later, in sporadic adenomas, there is evidence of growth down into adjacent crypts—"top-down".


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