Neurotensin Receptor 1 (NTSR1) Is Preferentially Expressed in Glandular Element of Intestinal Tumors with Neuroendocrine Differentiation.
Xianyong Gui, Yunru Li, Shuhong Liu, Zu-Hua Gao. University of Calgary, AB, Canada
Background: Neurotensin (NT) is a gut neuroendocrine peptide with diverse functions including trophic effects. Most of NT's effects are mediated via the high-affinity neurotensin receptor 1 (NTSR1), a member of G-protein-coupled receptor family. Both NT and NTSR1 express in several carcinomas as well as neuroendocrine tumors. In GI tract, certain tumors, e.g., goblet cell carcinoids (GCCs) and glandular-endocrine mixed tumors (GEMTs), show dual differentiation with a presentation of mixed glandular and endocrine features. The expression pattern and oncogenic role of NTSR1 in this type of GI tumors are not yet understood. Here we studied whether NTSR1 expression shows a preference in one of the differentiations.
Design: NTSR1 expression was detected by immunohistochemistry in appendicieal GCCs (n=17, 8 M, 9 F, age 22-69 yo), appendiceal/ileal classic carcinoid tumors (CCTs) (n=10, 5 M, 5 F, age 13-86 yo), and colorectal GEMTs including composite tumors (n=12, 5 M, 7 F, age 39-85 yo) and collision tumors (n = 10, 5 M, 5 F, age 48-74 yo). Conventional colorectal adenocarcinomas (CRCs) without neuroendocrine features (n=12, 7 M, 5 F, age 42-85 yo) were included as an additional control. The intensity/degree of NTSR1 expression was semiquantitated (as negative, 1+, 2+, 3+). A comparison of NTSR1 expressions was analyzed between different tumors and between glandular and endocrine elements of GEMTs.
Results: Immunoreactivity of NTSR1 appeared in a cytoplasmic granular pattern. As compared with CCTs, GCCs showed a significantly higher positivity (94.1% vs 70%, p < 0.05) and higher intensity (2+, 35.3% vs 0%, p < 0.05) of NTSR1 expression. 5 GCCs with marked adenocarcinoma-like pattern all showed a 2+ to 3+ expression. In GEMTs, the collective positivity of NTSR1 is significantly higher in glandular elements than that in endocrine elements (70.6% vs 38.1%, p < 0.05), and the difference seems to exist mainly in collision tumors as compared with composite tumors. In composite tumors both glandular and endocrine tumor cells showed a similar positivity. In comparison, all CRCs showed an outstandingly higher level expression (90% with 3+, 10% with 2+).
Conclusions: In various intestinal tumors, NTSR1 expression is significantly stronger in the tumor cells with glandular differentiation than in that with neuroendocrine differentiation. Our data suggests that NTSR1 is preferentially involved in the carcinogenesis and/or progression of adenocarcinomas. This finding may have therapeutic implication.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 223, Wednesday Morning