Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission

Sean L Preston, Wai-Man Wong, Annie On-On Chan, Richard Poulsom, Rosemary Jeffery, Robert A Goodlad, Nikki Mandir, George Elia, Marco Novelli, Walter F Bodmer, Ian P Tomlinson, Nicholas A Wright

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 champions 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. Serial sections of 40 small (<3 mm) sporadic colorectal adenomas were stained with H&E, MIB-1, and for beta-catenin. 10 early adenomas were Feulgen-stained and microdissected. We also examined the flat mucosa of three patients who had undergone colectomies for familial adenomatous polyposis (FAP) and specimens from a XO/XY individual with FAP, the latter using in situ hybridization for the Y chromosome. In the earliest sporadic adenomas, there were crypts entirely filled with adenomatous epithelium, which showed proliferative activity and nuclear localization of beta-catenin. There was a sharp cutoff between crypt epithelial cells showing nuclear beta-catenin and surface cells with membrane staining. In slightly larger lesions, adenomatous spread from above was seen. Microdissected adenomas showed multiple fission events, with proliferation distributed equally 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. 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).

Original languageEnglish
Pages (from-to)3819-25
Number of pages7
JournalCancer Research
Issue number13
Publication statusPublished - 1 Jul 2003

Keywords / Materials (for Non-textual outputs)

  • Adenoma/pathology
  • Adenomatous Polyposis Coli/pathology
  • Colonic Neoplasms/pathology
  • Colonoscopy
  • Dissection/methods
  • Humans
  • Intestinal Mucosa/cytology


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