Ghrelin, a recently discovered
peptide isolated from the gastric corpus mucosa, is believed to be important in the regulation of
growth hormone secretion and has been shown to increase appetite and food intake as well. It may also have other gastrointestinal and cardiac functions. Because a cell of origin for
ghrelin has not been convincingly identified in the gastric mucosa thus far, we studied the immunohistochemical expression of
ghrelin in proliferative lesions of the enterochromaffin-like (ECL) cells-a cell that is not only exclusively confined to the gastric corpus mucosa but is its dominant endocrine cell type as well.
Formalin-fixed,
paraffin embedded tissues from three cases of gastric ECL cell
hyperplasia and five ECL
carcinoids (three with coexisting foci of diffuse, linear, and micronodular
hyperplasia) were immunohistochemically stained for
ghrelin, using a commercially available antibody. The Sevier-Munger
stain for ECL cells and immunohistochemical stains for
chromogranin,
gastrin,
serotonin,
somatostatin, and vesicular monoamine transporter-2 (VMAT-2) were performed on parallel sections for correlation with the
ghrelin staining results. All ECL cell
carcinoids and hyperplastic lesions were positive for both the Sevier-Munger and the immunohistochemical stains for
chromogranin and VMAT-2. Immunoreactivity for
ghrelin was seen in 4/5 ECL
carcinoids, all cases of ECL cell
hyperplasia, as well as in all areas with linear and micronodular
hyperplasia adjacent to the ECL cell
carcinoids. In each instance, such staining was confined to the Sevier-Munger, and VMAT-2 positive cells only. Our findings indicate that the ECL cells are either the
ghrelin-producing cells of the gastric mucosa or acquire the capability to synthesize
ghrelin during proliferative states encompassing the entire
hyperplasia to
neoplasia spectrum. In view of the orexigenic and other known actions of
ghrelin, the functional and/or
biologic significance of
ghrelin production in such ECL cell proliferations needs to be investigated further.