Expression of vesicular monoamine transporters in endocrine hyperplasia and endocrine tumors of the oxyntic stomach

Background: Gastric enterochromaffin-like (ECL) cells selectively express t he vesicular monoamine transporter (VMAT) VMAT2, and enterochromaffin (EC) cells the VMAT1 isoform. Aims: We investigated whether VMAT isoform selecti on indicates the origin of endocrine hyperplasia and neoplasia from oxyntic ECL or EC cells and may be of prognostic significance in different types o f gastric carcinoids. Methods: Tissue from patients with chronic atrophic g astritis (CAG), Zollinger-Ellison-syndrome (ZES), gastric carcinoids and ne uroendocrine carcinoma (NEC) was investigated by immunohistology and in sit u hybridization. Results: Endocrine cells forming diffuse, linear, and micr onodular hyperplasia in CAG and ZES, as well as oxyntic microcarcinoids exp ressed both VMAT2 and chromogranin A (CgA) but neither VMAT1 nor serotonin. In five of six sporadic carcinoids VMAT2 and CgA but not VMAT1 were detect ed. One carcinoid was copositive for VMAT1 and serotonin but negative for V MAT2. Electron microscopy confirmed the VMAT2-positive tumors as ECLoma and the VMAT1 -immunoreactive carcinoid as EComa. Conclusions: VMAT2 and VMAT1 are reliable markers for differentiation of gastric endocrine hyperplasia and neoplasia from ECL and EC cells, respectively. The significance of VMAT 2 and VMAT1 as prognostic markers lies in the relatively poor prognosis for EComa compared to ECLoma, characterized by VMAT2 positivity. The absence o f both VMAT2 and VMAT1 in NEC may indicate poor prognosis.