Neurotensin Receptor 1 (NTSR1) Expression in Inflammatory Bowel Diseases (IBD): Association with Mucosal Inflammation and Dysplasia/Neoplasia.
Xianyong Gui, Shuhong Liu, Zu-Hua Gao. University of Calgary, AB, Canada
Background: Neurotensin (NT), a 13-AA gut peptide, acts as paracrine and endocrine modulator of various gut functions. Most of NT's effects are mediated through high-affinity neurotensin receptor 1 (NTSR1), a member of G-protein-coupled receptor family. NT/NTSR1 signaling was found to be proinflammatory as well as proregenerative in colonic inflammation. NTSR1 is also involved in the tumorigenesis and progression of colonic carcinoma, mainly via its link with Wnt/APC/Tcf/β-catenin pathway. It is our hypothesis that NTSR1 in colonic epithelium is upregulated in IBD and NTSR1 overexpression plays a role in the development of colitis-associated dysplasia/neoplasia.
Design: 18 colectomy cases of long-standing IBD (13 UC, 3 CD, 2 IC, 14 M, 4 F, age 26-84 yo) were retrieved from our pathology file. Of each case, tissue blocks were selected from those with proven histology of normal (3), active colitis (16), inactive colitis (14), raised low-grade dysplasia (LGD, 16), high-grade dysplasia (HGD, 3), and adenocarcinoma (CA, 8). Of LGD lesions, a distinction between dysplasia-associated lesion or mass (DALM, i.e., sessile full-thickness dysplasia, colitis-associated, 12) and adenoma-like dysplastic polyps (ALDP, i.e., 'top-down' pattern dysplasia, likely sporadic adenoma, 4) was attempted based on current morphological criterion. NTSR1 expression was detected by immunohistochemistry, and it was semiquantitated (as negative, 1+, 2+, and 3+).
Results: Immunoreactivity of NTSR1 appeared in a cytoplasmic pattern. NTSR1 was not detected in normal mucosa but was expressed similarly in both active and inactive colitis. LGD showed a significantly stronger expression as compared with non-dysplastic colitic mucosa, with most cases showing a ≥ 2+ intensity (81.25% vs 32.26%, p = 0.001) but less cases showing a 1+ intensity (18.75% vs 64.52%, p = 0.07). However, no significant difference existed between DALM and ALDP. CA or combined CA/HGD showed a further stronger expression, with more cases showing a 3+ intensity than that in LGD of both DALM and ALDP (62.50% vs 12.50% for CA vs LGD, p = 0.037; 63.64% vs 12.50% for CA/HGD vs LGD, p = 0.021).
Conclusions: Both active and inactive colitis upregulate NTSR1 of colonic epithelium. Low to high-grade dysplasia and carcinoma are associated with a step-wisely higher expression. The overexpression shows a similar pattern in both colitis-associated and sporadic dysplasia, which suggests that NTSR1 may be equally involved in these two dysplastic/neoplastic processes.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 219, Wednesday Morning