Aberrant gastric apomucin expression in ulcerative colitis and associated neoplasia

To evaluated the presence of gastric metaplasia in colonic mucosa of patients with ulcerative colitis and its relationship with dysplasia/neoplasia.

Ninety patients with UC were selected. The duration and the extent of disease were registered in all the cases. Biopsies were histologically and immunohistochemically assessed. Crypt distortion, goblet cell depletion, Paneth cell metaplasia and inflammatory activity were graded, as well as dysplasia and invasive neoplasia (absent or present). Monoclonal antibodies against the gastric apomucins MUC5AC (foveolar) and MUC6 (mucopeptic) were used.

Neoplasia was observed in 16 patients, 8 non-invasive (dysplasia) and 8 invasive (adenocarcinoma). MUC5AC and MUC6 were detected in 63 and 16 out the 90 cases, 70.0% and 17.8%, respectively. The staining was patchy for both antibodies, affecting groups of cells more often than isolated cells. The presence of MUC5AC correlated positively with inflammatory activity and goblet cell depletion (R=0.231, p=0.03 and R=0.211, p=0.048, respectively). The expression of MUC6 correlated positively with age (R=0.297, p=0.005), duration of disease (R=0.287, p=0.008), extent of disease (R=0.342, p=0.001), crypt distortion (R=0.276, p=0.01) and the presence of neoplasia (R=0.483, p<0.00). There was no correlation between Paneth cell metaplasia and apomucin expression.

Our study demonstrates the aberrant expression of gastric apomucins in UC and suggests that MUC5AC is associated with inflammation while MUC6 is related to the presence of neoplasia. The demonstration of metaplastic cell lineages preceding dysplasia supports the biological link between inflammation and neoplasia, MUC6 emerging as a putative biomarker of dysplasia in ulcerative colitis patients.