Immunophenotype of sporadic and familial adenomatous polyposis associated fundic gland polyps: a mucin and MIB1 study

Abstract

Background: Fundic Gland Polyps (FGPs) are small sessile (2-5 mm) usually multiple polyps arising in the gastric, acid-secreting mucosa, described both in a sporadic form, prevalently in middle aged females, and associated with familial adenomatosis coli (FAP)-Gardner's syndrome and their attenuated variants (syndromic form).

Aims: We performed an immunohistochemical study on 5 syndromic (4 cases without and 1 case with dysplasia) and 28 sporadic FGPs, using monoclonal antibodies (MoAbs) against normal epitopes of fundic mucosa (Ck20, the surface gastric mucin M1, EMA, ChA), H. pylori and HLA-DR(Ia) antigens, CEA and mucin epitopes, and the Ki67 (MIB1) proliferation antigen, in order to establish the immunophenotype of FGPs; find any possible differences between sporadic and syndromic polyps.

Results: Ck20 and M1 were positive on surface and foveolar epithelium of controls, whereas sporadic and syndromic FGPs showed an enhanced deep positivity below foveolar necks ("foveolar metaplasia"); EMA was strongly positive on parietal cells, highlighting intracytoplasmic canaliculi. Chromogranin-positive cells in FGPs were alike controls, except for a sporadic case with micronodular hyperplasia. Ck7, as expected, was negative in controls, whereas the 5 syndromic FGPs and 25 of 28 sporadic FGPs showed a diffuse superficial and deep expression. H. pylori anti-serum gave negative results on all cases, and only 3 sporadic FGPs showed epithelial expression of HLA-DR(Ia). Syndromic FGPs were CEA negative, whereas 32% of sporadic FGPs expressed it. FGPs showed a neoexpression of the mucin oncofetal epitopes syalil-Tn (3/5 syndromic, 82% sporadic) CA19.9 and CA50 (4/5 syndromic, 14% sporadic). MIB1-labelling index of surface (30.5%) and deep (37.1%) compartments of the 4 syndromic FGPs without dysplasia was enhanced, with high statistical significance (p < 0.0001) both in comparison to controls (16.9% superficial stain only) and sporadic FGPs (15.8% surface, 19.5% deep labeling indexes). Moreover, the MIB1 labeling-index of the syndromic case with dysplasia (60.8% surface, 56.6% deep labeling indexes) was further enhanced in comparison with the other 2 syndromic cases.

Conclusions: Sporadic and syndromic FGPs showed a neoexpression of Ck7, CEA, and mucin epitopes. As these markers are normal antigens of fetal stomach, FGPs showed a fetal, "immature" immunophenotype. The only difference we found between syndromic and sporadic polyps was a statistically significant enhanced MIB1-labelling index expression by syndromic FGPs, further enhanced in the syndromic FGP with dysplasia.