Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours

Neuroendocrine tumours are characterized by their capacity to produce hormo nes, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VM AT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal ori gin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoid s) expressed predominantly VMAT1, while histamine-producing endocrine tumou rs (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-prod ucing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorec tal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestin al endocrine tumours, with a pattern specific for each tumour type, reflect ing their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may th erefore become valuable markers in the classification of I neuroendocrine t umours and may also indicate patients suitable for radioisotope treatment o perating via these transporter systems. Copyright (C) 2001 John Wiley & Son s, Ltd.