Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study.
The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Eissele
R
R
Abteilung für Gastroenterologie und Stoffwechselkrankheiten, Philipps-Universität, Marburg, Germany.
Göke
R
R
Weichardt
U
U
Fehmann
H C
HC
Arnold
R
R
Göke
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D004701:Endocrine Gland Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*
D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon