The Expression of Glucagon-Like Peptide-1 Receptor and Dipeptidyl Peptidase-IV in Neuroendocrine Neoplasms of the Pancreas and Gastrointestinal Tract

Neuroendocrine neoplasm (NEN) of the pancreas and gastrointestinal tract is infrequent but often produces hormones to cause distinct clinical features. Glucagon-like peptide-1 receptor (GLP1R) is a G-protein coupled receptor for GLP1, which is cleaved by dipeptidyl peptidase (DPP)-IV, a peptidase that regulates the activity of peptide hormones. Since these molecules are involved in the neuroendocrine function of NEN, they could serve molecular targets for diagnosis and therapy of NEN. However, the expressions of these molecules in NEN are not well studied. We therefore examined the expression of GLP1R and DPP-IV in 22 cases of pancreatic NEN (P-NEN) and 20 cases of gastrointestinal NEN (GI-NEN) by immunostaining. GLP1R was expressed in all eight insulinomas (100 %) but so in only four out of 14 cases (29 %) of non-insulinomas. In contrast to GLP1R, DPP-IV was detected in one out of eight insulinomas (13 %) and in 12 out of 14 cases (86 %) of non-insulinomas. In GI-NEN, GLP1R was negative in all 10 cases of the foregut NEN, whereas it was expressed in all three cases (100 %) of midgut NEN and four out of seven cases (57 %) of hindgut NEN. DPP-IV was expressed in five out of 10 cases (50 %) of the foregut NEN. The expression was detected in two out of three cases (67 %) of midgut NEN and in all seven cases (100 %) of hindgut NEN. In conclusion, we found distinct expression patterns of GLP1R and DPP-IV depending on the neuroendocrine cell types in P-NEN and the anatomical sites in GI-NEN.