To elucidate the contribution of beta-catenin gene mutation to the histogenesis of sporadic FGP, we analyzed beta-catenin gene mutation in exon 3 in 45 FGP lesions obtained from 35 patients.
The fundic gland polyps were histologically and genetically identical to single sporadic fundic gland polyps and demonstrated frequent somatic activating mutations in exon 3 of the beta-catenin gene.
Interestingly, in the remaining polyp, we found an activating beta-catenin gene mutation whereas no such mutations were detected in FGPs of patient No II.
SFRPs, APC, and AXIN2 were more frequently methylated in GNCCPs and CGAs (SFRP1, 88%/96%; SFRP2, 85%/93%; SFRP4, 73%/81%; APC, 81%/81%; AXIN2, 81%/85%; respectively) than in FGPs and FGP-Ds (37%/50%; 41%/42%; 41%/58%; 37%/33%; 41%/50%; respectively).
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.
FAP-associated FGPs arise through somatic second hit alterations of the adenomatous polyposis coli (APC) gene and frequently demonstrate epithelial dysplasia (Am J Pathol 2000, 157:747-754).
We have recently shown that somatic adenomatous polyposis coli (APC) gene alterations are frequently present in FGPs associated with familial adenomatous polyposis (FAP), raising the possibility that mutations of the beta-catenin gene affecting the APC/beta-catenin pathway might be involved in the pathogenesis of sporadic FGPs.
Furthermore, there was no difference in the frequency of somatic APC gene alterations between FGPs with foveolar dysplasia (10 of 20, 50%), indefinite for dysplasia (four of six, 67%), and nondysplastic (seven of 15, 47%) in FAP patients (P: = 0.697).
Moreover, the presence of somatic APC mutations in fundic gland polyps suggests that inactivation of the APC gene plays a role not only in forming adenomas but also in forming hyperplastic polyps in fundic gland mucosa, and there may be some additional steps to the adenoma-carcinoma sequence.
To investigate this hypothesis, we examined proliferative activity, degree of apoptosis, beta-catenin expression and p53 expression in syndromic and sporadic FGPs.
A total of 196 biopsy specimens of FGPs, which consisted of 87 FGPs in patients treated with PPIs (PPI group) and 109 FGPs in patients treated without PPIs (non-PPI group) were compared histologically using haematoxylin and eosin staining, Ki67 immunohistochemistry and multiplex immunohistochemical stain with Ki67, MUC5AC and MUC6.