Loss of extracellular E-cadherin in the normal mucosa of duodenum and colon of patients with familial adenomatous polyposis.
The duodenum is the main site for (pre-) malignant extracolonic manifestations in patients with familial adenomatous polyposis (FAP). Changes in the E-cadherin/beta-catenin complex play a pivotal role in the development of malignancies. Loss of E-cadherin has been described in association with loss of SMAD4. To elucidate the pathways leading to the development of duodenal adenomas in patients with FAP, the distributions of E-cadherin, SMAD4, and beta-catenin were analyzed. Furthermore, differences between the duodenum and colon were evaluated. Normal FAP duodenum (n = 13) and FAP duodenal adenomas (n = 50; total, 21 patients) were compared with non-FAP duodenal adenomas (n = 7) and normal non-FAP duodenum (n = 15) by immunohistochemical staining for extracellular and intracellular E-cadherin, beta-catenin, and SMAD4. Colonic biopsies of 10 patients with FAP were also studied, as well as non-FAP colonic adenomas (n = 26) and non-FAP normal colon (n = 12). Compared with the intracellular component of E-cadherin that was present in all cases, a significant loss of extracellular E-cadherin was observed in both duodenal and colonic adenomas and normal tissue of patients with FAP. Nuclear localization of beta-catenin was more often observed in duodenal FAP adenomas compared with non-FAP adenomas. Loss of nuclear SMAD4 was seen in the duodenum and, to a higher degree, in the colon of patients with FAP, as well as non-FAP patients. The loss of extracellular E-cadherin in the normal duodenal and colonic mucosa of patients with FAP might play a role in the high susceptibility of these tissues for (pre-) malignant transformation.
Berkhout
Marloes
M
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.berkhout@mdl.umcn.nl
Gosens
Marleen J E M
MJ
Brouwer
Katrien M
KM
Peters
Wilbert H M
WH
Nagengast
Fokko M
FM
van Krieken
J Han J M
JH
Nagtegaal
Iris D
ID
D000236:Adenoma / Q000473:pathology / Q000503:physiopathology; D011125:Adenomatous Polyposis Coli / Q000473:pathology / Q000503:physiopathology*; D015820:Cadherins / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000473:pathology; D004379:Duodenal Neoplasms / Q000473:pathology; D004386:Duodenum / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D051901:Smad4 Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D051176:beta Catenin