Expression of vesicular monoamine transporters in endocrine hyperplasia and endocrine tumors of the oxyntic stomach.
BACKGROUND
Gastric enterochromaffin-like (ECL) cells selectively express the vesicular monoamine transporter (VMAT) VMAT2, and enterochromaffin (EC) cells the VMAT1 isoform.


OBJECTIVE
We investigated whether VMAT isoform selection indicates the origin of endocrine hyperplasia and neoplasia from oxyntic ECL or EC cells and may be of prognostic significance in different types of gastric carcinoids.


METHODS
Tissue from patients with chronic atrophic gastritis (CAG), Zollinger-Ellison-syndrome (ZES), gastric carcinoids and neuroendocrine carcinoma (NEC) was investigated by immunohistology and in situ hybridization.


RESULTS
Endocrine cells forming diffuse, linear, and micronodular hyperplasia in CAG and ZES, as well as oxyntic microcarcinoids expressed both VMAT2 and chromogranin A (CgA) but neither VMAT1 nor serotonin. In five of six sporadic carcinoids VMAT2 and CgA but not VMAT1 were detected. One carcinoid was copositive for VMAT1 and serotonin but negative for VMAT2. 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 VMAT2 and VMAT1 as prognostic markers lies in the relatively poor prognosis for EComa compared to ECLoma, characterized by VMAT2 positivity. The absence of both VMAT2 and VMAT1 in NEC may indicate poor prognosis.
Eissele
R
R
Department of Gastroenterology and Endocrinology, Institute of Anatomy and Cell Biology, Philipps University, Marburg, Germany.
Anlauf
M
M
Schäfer
M K
MK
Eiden
L E
LE
Arnold
R
R
Weihe
E
E
D000328:Adult; D000368:Aged; D015306:Biogenic Monoamines / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology; D004759:Enterochromaffin Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000378:metabolism* / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015043:Zollinger-Ellison Syndrome / Q000378:metabolism* / Q000473:pathology
D015306:Biogenic Monoamines