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The development of duodenal microadenomas in FAP patients: the human correlate of the Min mouse
Author(s) -
Preston SL,
Leedham SJ,
Oukrif D,
Deheregoda M,
Goodlad RA,
Poulsom R,
Alison MR,
Wright NA,
Novelli M
Publication year - 2008
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2294
Subject(s) - familial adenomatous polyposis , crypt , adenoma , biology , pathology , tubular adenoma , villin , carcinogenesis , cancer research , medicine , colorectal cancer , cancer , endocrinology , genetics , colonoscopy , actin
The morphological changes associated with the adenoma‐carcinoma sequence are well documented in the colorectum. Small intestinal carcinogenesis is thought to progress through a similar adenoma‐to‐carcinoma pathway, but there is a relative dearth of studies examining the associated morphological changes. The best‐known mouse model of intestinal neoplasia, the multiple intestinal neoplasia (Min) mouse, has been criticized as a genetic model of intestinal neoplasia, as the majority of its tumours occur in the small intestine. We examined pancreatico‐duodenal resection specimens from seven familial adenomatous polyposis (FAP) patients. Serial sections of these were stained with haematoxylin and eosin for β‐catenin and its downstream target CD44, for BMPR1a, lysozyme, carbonic anhydrase II, and with MIB‐1. Individual dysplastic crypts were isolated and mutations in the FAP ( APC ) gene compared between the top and bottom of the crypt. We found that: (a) duodenal microadenomas are extremely common in FAP patients; (b) these grow in the core of duodenal villi, forming lesions similar to those described in the Min mouse; (c) many lesions arise as monocryptal adenomas and grow by a process of crypt fission and branching; (d) migrating adenomatous cells lose their dysplastic phenotype as they migrate up the crypt villous axis; and (e) Paneth cells lose positional information. In conclusion: (a) the morphological similarity of adenomas in the Min mouse and human suggest the Min mouse is a good model of FAP; (b) duodenal adenomas in FAP originate in monocryptal adenomas and follow the ‘bottom‐up’ rather than the ‘top‐down’ model of morphogenesis; (c) early microadenomas show evidence of cellular differentiation; (d) defects in the positioning of Paneth cells suggests disruption of the EphB2:EphB3 receptor system. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.