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Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.ORCID iD: 0000-0002-9198-4193
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2015 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 47, 13240-13249 p.Article in journal (Refereed) Published
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Abstract [en]

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-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients.

RESULTS:

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 cell population 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-MeImAA 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. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

Place, publisher, year, edition, pages
2015. Vol. 21, no 47, 13240-13249 p.
Keyword [en]
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
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:uu:diva-274442DOI: 10.3748/wjg.v21.i47.13240ISI: 000366889600004PubMedID: 26715806OAI: oai:DiVA.org:uu-274442DiVA: diva2:896482
Available from: 2016-01-21 Created: 2016-01-21 Last updated: 2017-11-30Bibliographically approved

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Tsolakis, Apostolos V.Grimelius, LarsStridsberg, MatsJanson, Eva T.

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