Patients with
inflammatory bowel disease (IBD) are at increased risk of developing colorectal
adenocarcinoma. The factors that result in IBD-associated
carcinogenesis are not understood. We hypothesized that altered expression of intestinal epithelial
tight junction proteins might contribute to neoplastic progression. Semiquantitative immunohistochemical staining of human biopsies was used to assess expression of the
tight junction proteins claudin-1,
claudin-2,
claudin-4, and
occludin in IBD, IBD-associated dysplasia, acute, self-limited
colitis (ASLC), and sporadic
adenomas.
Claudin-1 and
claudin-2 expression was elevated in active IBD,
adenomas, and IBD-associated dysplasia, but not ASLC. In contrast,
claudin-4 expression was elevated in both active IBD and ASLC.
Occludin expression was similar to control in all cases. Importantly, in IBD,
claudin-1 and
claudin-2 expression correlated positively with inflammatory activity. To investigate mechanisms underlying altered
claudin expression,
beta-catenin activation was assessed as nuclear localization. Like
claudin-1 and
claudin-2,
beta-catenin was markedly activated in IBD, sporadic dysplasia, and IBD-associated dysplasia, but was only slightly activated in ASLC. Taken together, these data suggest that
beta-catenin transcriptional activity is elevated in chronic injury and that this may contribute to increased
claudin-1 and
claudin-2 expression. We speculate that increased
claudin-1 and
claudin-2 expression may be involved at early stages of transformation in IBD-associated
neoplasia.