Mucin gene expression in the ileoanal reservoir is altered and may be relevant to the risk of inflammation and dysplasia

Background: Adaptive colonic phenotypic change of the ileal mucosa is a feature of the ileoanal reservoir (IAR) with time, as described by mucin glycoprotein and histological analysis. Mucin gene expression is altered in colorectal neoplasia and inflammatory bowel disease but little is known of its expression in the IAR. Aims: To examine the changes in mucin gene expression contributing to mucosal protection of the IAR against a background of known changes occurring in inflammatory disease and colorectal neoplasia. Patients: Paraffin embedded specimens from 29 "W" and 11 "J" ileoanal reservoirs were studied. Colonic and ileal control tissue was obtained from normal resection margins. Methods: Mucin mRNA was detected by in situ hybridisation using [S-35]dATP labelled oligonucleotide probes. Mucin core protein was detected by immunohistochemistry. Results: There was no change in mRNA expression of MUC1-4 in the IAR compared with ileal controls but there was a decrease in the protein product of MUC1 and MUC3. No mRNA transcripts of MUC5AC, 5B, or 6 were detected but protein product of MUC5AC and MUC6 was detected. Both cases of MUC6 positivity and 115 cases of MUC5AC positivity were confined to the ulcer associated cell lineage. No dysplasia was detected. Conclusions: There is a change in the pattern of the membrane associated mucins MUC1 and MUC3, part of which is in keeping with changes described in colorectal neoplasia. A small number of cases demonstrated mucin gene changes (MUC5AC) which are seen in early neoplasia and this may provide a valuable monitor for such changes in IAR surveillance.