MUC1 is an epithelial cell mucin that normally plays a protective role against inflammation. In cases of chronic inflammation and cancer, there is overexpression of the abnormal hypoglycosylated MUC1 form. We studied the role of hypoglycosylated MUC1 as a driver of chronic inflammation and progression to colitis associated colon cancer (CACC) in mouse models of IBD. We previously found that MUC1 expression increases and glycosylation decreases as the disease progresses. A vaccine against abnormal hypoglycosylated MUC1 administered early in life ameliorates IBD and prevents progression to CACC in mice that spontaneously develop IBD. In this study we aimed to evaluate if abnormal MUC1 expression is characteristic of human IBD. In particular, we were interested in MUC1 expression in recurrent postoperative Crohn's disease (CD) and association with endoscopic (Rutgeerts) activity scores (i0–i4). We hypothesized that abnormal MUC1 expression is associated with endoscopic postoperative Crohn's disease recurrence.Methods:
We obtained archived neo-terminal ileum endoscopic biopsies from postoperative CD patients who had previously undergone “curative” intestinal resection for isolated Crohn's disease. All patients had endoscopic ileal Rutgeerts scores recorded at time of their colonoscopy. Scores were either i0 (normal), i1 (≤5 aphthous ulcers), i2 (>5 aphthous ulcers), i3 (diffuse aphthous ileitis), or i4 (diffuse inflammation with already large ulcers, nodules and/or narrowing). Consecutive tissue sections were stained with 2 different anti-MUC1 antibodies: HMPV that recognizes both normal and abnormal MUC1 and 4H5 that recognizes only the abnormal MUC1. Level of expression was determined by the intensity of staining.Results:
Thirty-five postoperative CD patients were analyzed. Of these patients, 15 had an ileal score of i0, 7 were i1, 10 were i2, and 3 had a score of i4. Fourteen of 15 patients (93.3%) in the i0 group expressed very low levels of MUC1 but no abnormal form, whereas 1 patient had a higher MUC1 expression with most in abnormal form. Of the 7 i1 patients, 4 expressed low levels of MUC1, and 3 patients had high MUC1 expression; 2 of these 3 patients expressed the abnormal MUC1 form. Five patients with an i2 score had a heterogeneous MUC1 pattern with 5 expressing very high levels of abnormal MUC1. All i4 patients had high levels of MUC1 and most in the abnormal form.Conclusions:
Abnormal MUC1 expression is associated with endoscopic postoperative CD recurrence (i2–i4). The role of abnormal MUC1 expression in postoperative Crohn's disease is not clear, but may be associated with recurrence and disease progression. Further study is underway to explore the pathogenesis of MUC1 in postoperative CD.