We looked for
opioid peptides and their precursors in 108
tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-
opioid" antibody, 3-E7, which recognizes the tetrapeptide
Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known
opioid peptides), in conjunction with polyclonal
antibodies directed against representative
peptides of each of the three precursors (
alpha-endorphin, [
met]enkephalin-Arg-
Gly-Leu, and
dynorphin B). Using the
avidin-
biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal
pheochromocytomas, all of 6 thyroid
medullary carcinomas, and all of 5
pituitary adenomas.
Opioid staining was also observed in
parathyroid adenomas (8 of 9),
pancreatic islet-cell tumors (7 of 10),
carcinoid tumors from various sites (18 of 26), and
paragangliomas (1 of 2). There was no immunoreactivity in pulmonary
small-cell carcinomas, Merkel-cell
tumors of skin,
neuroblastomas, or any of the non-
neuroendocrine tumors examined. The expression of
alpha-endorphin, [
met]enkephalin-Arg-
Gly-Leu, and
dynorphin B varied from
tumor to
tumor; however, positive staining with the "pan-
opioid" antibody was found in each
tumor containing at least one of the three precursors.
Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that
opioid expression within
tumors is most likely due to enhanced expression of a normal cell product and that
opioid peptides are useful markers of neuroendocrine differentiation in many
tumors.