Abnormal MUC1 Expression in Post-operative Crohnʼs Disease Recurrence

Abstract

Introduction: Glycoprotein MUC1 is an epithelial cell mucin that contributes to mucosal homeostasis and normally plays a protective role against inflammation. Hypoglycosylated abnormal from of MUC1, on the other hand, promotes chronic inflammation and cancer progression. We studied the role of hypoglycosylated MUC1 as a driver of chronic inflammation in IBD 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 to i4). We hypothesized that abnormal MUC1 expression would occur at the anastomosis and promote disease progression and that it might or might not parallel patterns of CD endoscopic recurrence.Figure 1Methods: We obtained archived neo-terminal ileum biopsies from postoperative CD pts who had endoscopic Rutgeerts scores recorded. 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 intensity of staining. Results: Fifteen postoperative CD pts were analyzed; 7 with an ileal score of i0, 5 with i2, and 3 with i4. Six pts in the i0 group expressed very low levels of MUC1 but no abnormal form, whereas 1 pt had a higher MUC1 expression with most in abnormal form. Three pts with an i2 score had heterogeneous MUC1 pattern with 2 expressing very high levels of abnormal MUC1. All i4 pts had high levels of MUC1 and most in the abnormal form. (Fig) Conclusion: Our preliminary data suggest that abnormal MUC1 expression in postoperative CD recurrence, with few exceptions, is associated with a worse endoscopic score. We continue to examine a much larger number of biopsies focusing especially on those where the level of abnormal MUC1 expression does not associate with the endoscopic score. A combination of endoscopic score with level of abnormal MUC1 expression could be a better predictor of disease progression. A postoperative MUC1 vaccine study to prevent postoperative CD recurrence is being planned.