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Obestatin/ghrelin cells in normal mucosa and endocrine tumours of the stomach

¹ Section of Endocrine Oncology, Department of Medical Sciences, Departments of² , Clinical Chemistry³ Genetics and Pathology, University Hospital, 751 85 Uppsala, Sweden⁴ Department of Pathology, the St Olav University Hospital, Trondheim 7006, Norway⁵ Department of Clinical Pathology and Cytology, the Ryhov County Hospital, Jönköping 551 85, Sweden⁶ Department of Gastroenterology, the St Olav University Hospital, Trondheim 7006, Norway

(Correspondence should be addressed to A V Tsolakis; Email: apostolos.tsolakis{at}medsci.uu.se)

Objective: Obestatin and ghrelin are derived from the same gene and co-expressed in the same endocrine cells. Vesicular monoamine transporter-2 (VMAT-2), a marker for enterochromaffin-like (ECL) cells, is considered to be expressed in ghrelin cells. The aim was to establish if the two peptides and the transporter are co-expressed, both in normal gastric mucosa and in gastric endocrine tumours.

Design: An immunohistochemical study was performed on gastric biopsy material and on surgical specimens from 63 patients with gastric endocrine tumours and from individuals with normal gastric mucosa. Cells displaying obestatin immunoreactivity were examined regarding co-localization with ghrelin and VMAT-2. Both single- and double-immunostaining techniques were applied. Obestatin concentration in blood was measured in a subgroup of these patients. The results were correlated to various clinico-pathological parameters.

Results: In the normal mucosa, obestatin/ghrelin-immunoreactive cells rarely co-expressed VMAT-2. In most tumour tissue specimens, only a fraction of neoplastic cells displayed immunoreactivity to obestatin, and these cells always co-expressed ghrelin. Neoplastic obestatin-/ghrelin-IR cells invariably expressed VMAT-2, except for two ghrelinomas. The obestatin concentrations in blood were consistently low and did not correlate to clinico-pathological data.

Conclusions: Obestatin and ghrelin immunoreactivity always occurred in the same endocrine cells in the gastric mucosa but these cells only occasionally co-expressed VMAT-2, opposite to the findings in tumours. These results indicate that endocrine cells expressing obestatin and ghrelin mainly differ from VMAT-2 expressing cells (ECL-cells) and can develop into pure ghrelinomas. Plasma concentrations of obestatin did not correlate to cellular expression.