Dysplasia in fundic gland polyps is associated with nuclear beta-catenin expression and relatively high cell turnover rates.
BACKGROUND
Fundic gland polyps (FGPs) occur in both syndromic and sporadic form. Syndromic FGPs arise through mutations in the adenomatous polyposis coli (APC) gene, whereas sporadic FGPs are caused by beta-catenin gene mutations. Dysplasia in sporadic FGPs, found less often than in syndromic FGPs, was recently associated with APC rather than beta-catenin mutations. These data suggest different functional consequences of APC and beta-catenin mutations. To investigate this hypothesis, we examined proliferative activity, degree of apoptosis, beta-catenin expression and p53 expression in syndromic and sporadic FGPs.


METHODS
Syndromic FGPs (n = 9) from familial adenomatous polyposis (FAP) patients and sporadic FGPs (n = 18) were studied. Proliferative activity, apoptotic cell death and expression of beta-catenin and p53 were examined by immunohistochemistry. In FGPs containing dysplasia, areas with and without dysplasia were compared.


RESULTS
Syndromic and sporadic FGPs without dysplasia exhibited similar proliferative activity, degree of apoptosis, beta-catenin and p53 expression. Dysplasia was observed more often in syndromic (4/9) than in sporadic FGPs (1/18). Within FGPs containing dysplasia, dysplastic areas showed abnormal nuclear beta-catenin staining in 3/5 cases and higher rates of cell proliferation and apoptosis than non-dysplastic areas. Overexpression of p53 was not observed.


CONCLUSIONS
The finding of similar rates of proliferation and apoptosis in syndromic and sporadic FGPs does not support the hypothesis that APC and beta-catenin gene mutations have different functional consequences in FGPs. The association of dysplasia with relatively high cell turnover rates and nuclear expression of beta-catenin indicates activation of the Wnt-APC-beta-catenin pathway in dysplasia. The finding of dysplasia in some but not all syndromic FGPs suggests the involvement of other genes in addition to the APC gene in the development of dysplasia in FGPs.
Jalving
M
M
Dept. of Gastroenterology and Hepatology, University Hospital Groningen, Groningen, The Netherlands.
Koornstra
J J
JJ
Boersma-van Ek
W
W
de Jong
S
S
Karrenbeld
A
A
Hollema
H
H
de Vries
E G E
EG
Kleibeuker
J H
JH
D017209:Apoptosis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011127:Polyps / Q000378:metabolism* / Q000473:pathology*; D013272:Stomach Diseases / Q000378:metabolism* / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin