neuropeptide-y and Gastrinoma

Sporadic gastrinoma is a pancreatic endocrine tumor whose ontogeny is unknown. The anatomic area where the vast majority of sporadic gastrinomas is found (pancreatic head region) corresponds topographically to the area traversed embryologically by the ventral pancreatic bud. Pancreatic polypeptide (PP), a 36-amino acid hormone, is secreted by pancreatic endocrine cells derived almost exclusively from the ventral pancreatic bud and is proposed as a marker for ventral bud derivation. Based on these observations we postulate that sporadic gastrinomas, found around the head of the pancreas, are derived from ventral bud tissue and should display a high incidence of PP immunoreactivity. Overall, we found PP immunoreactivity in 7 of 14 (50%) gastrinomas. Of those tumors located to the right of the superior mesenteric artery (SMA) (around the head of the pancreas), seven of nine (78%) contained PP, whereas no gastrinoma to the left of the SMA (n = 5) contained PP (p = 0.021; Fisher exact test). Only one other pancreatic endocrine or exocrine tumor, a glucagonoma located to the left of the SMA, stained positively for PP. We conclude that sporadic gastrinomas found around the head of the pancreas (to the right of the SMA) have a high incidence of PP immunoreactivity. These findings are consistent with our hypothesis that sporadic gastrinomas are derived from the ventral pancreatic bud.

Topics: Gastrinoma; Humans; Immunohistochemistry; Mesenteric Artery, Superior; Neuropeptide Y; Pancreatic Neoplasms; Pancreatic Polypeptide

Using an antiserum raised to the C-terminal region of neuropeptide Y (NPY) which does not cross-react with pancreatic polypeptide (PP), immunoreactivity has been detected in two different endocrine tumours of the human pancreas in concentrations permitting isolation and structural analysis. In a clinically-typical gastrinoma, resected from the head of pancreas, the concentration of NPY immunoreactivity was 3.4 nmol/g. Reverse phase HPLC analysis of extracts of this tumour resolved a single immunoreactive peptide coeluting with synthetic human NPY. The molecular mass of the isolated peptide, determined by mass spectroscopy, was 4270 Da, which was in close agreement with that derived from the deduced primary structure of human tumour NPY (4271.7 Da), obtained by gas-phase sequencing. A somatostatinoma, resected from the region of the ampulla of Vater, contained 3.8 nmol/g of NPY immunoreactivity and isolation of this immunoreactive peptide followed by structural analyses, indicated a molecular structure consistent with NPY 3-36. These data suggest that NPY immunoreactivity detected in human pancreatic endocrine tumours is molecularly heterogenous, a finding which may be of relevance in the symptomatology of such tumours as attenuation of the N-terminus of this peptide generates receptor selectivity.

Topics: Adult; Amino Acids; Chromatography, High Pressure Liquid; Gastrinoma; Humans; Male; Middle Aged; Molecular Weight; Neuropeptide Y; Pancreatic Neoplasms; Peptide Fragments; Radioimmunoassay; Somatostatinoma