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Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours

World Journal of gastroenterology 2015年第47期21卷 13240-13249页

作者： Apostolos V Tsolakis Lars grimelius göran granerus Mats Stridsberg Sture E Falkmer Eva T Janson Section of Endocrine Oncology Department of Medical SciencesUppsala University Section of genetics and Pathology Department of ImmunologyUppsala University Department of Medical and Health Sciences Linköping University Section of Biochemical Endocrinology Department of Medical SciencesUppsala University Department of Pathology Ryhov County Hospital

AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(gNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 ***: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these gNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with gNETs.

关键词： Enterochromaffin-like cells High performance liquid chromatography gastric neuroendocrine tumours Histidine decarboxylase Immunohistochemistry Urinary excretion of the main histamine metabolite methylimidazoleacetic acid Vesicular monoamine transporter 2

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