Ghrelin, an orexigenic
hormone, is normally produced mainly in stomach. In addition, it has been demonstrated in gastric
carcinoid tumors and less often in other
neuroendocrine tumors. We investigated
ghrelin expression by immunohistochemistry (
streptavidin-
biotin-
peroxidase complex method) in the full spectrum of resected
pituitary adenoma subtypes. Quantification of staining considered both the frequency of
ghrelin-reactive
tumor cells as well as their staining intensity. Cytoplasmic
ghrelin immunopositivity was identified in several
adenoma subtypes. Cellular staining varied considerably. In addition, the intensity of cell staining differed within the same
tumor and between
adenoma subtypes. The highest scores were noted in GH producing
adenomas exposed to long-acting
somatostatin analogs. In decreasing order, lower scores were encountered in
ACTH adenomas in
Cushing disease, silent subtype 3
adenomas, untreated GH
adenomas, silent
corticotroph adenomas of subtypes 1 and 2,
dopamine agonist-treated PRL
adenomas,
ACTH adenomas in
Nelson syndrome, and gonadotroph
adenomas. No significant immunoreactivity was noted in TSH, untreated PRL, and null cell
adenomas. The high immunoexpression of
ghrelin in GH
adenomas exposed to long-acting
somatostatin analogs remains unexplained, but may be due to either increased
ghrelin production or to suppression of its release. Based on our findings, it appears that
ghrelin immunopositivity does not serve as a
biomarker of
biologic behavior, prognosis and therapeutic responsiveness in
pituitary adenomas.