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

• Published in: World journal of gastroenterology : WJG 2015-12, Vol.21 (47), p.13240-13249
• Main Authors: Tsolakis, Apostolos V, Grimelius, Lars, Granerus, Göran, Stridsberg, Mats, Falkmer, Sture E, Janson, Eva T
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - enzymology; Adenocarcinoma - secondary; Adenocarcinoma - urine; Adult; Aged; Aged, 80 and over; Basic Study; Biomarkers, Tumor - urine; Chromatography, High Pressure Liquid; Enterochromaffin Cells - enzymology; Enterochromaffin Cells - pathology; Enterochromaffin-like cells; Female; Fluorescent Antibody Technique; Gastric neuroendocrine tumours; Ghrelin - analysis; High performance liquid chromatography; Histidine decarboxylase; Histidine Decarboxylase - analysis; Humans; Imidazoles - urine; Immunohistochemistry; Male; Middle Aged; Neuroendocrine Cells - enzymology; Neuroendocrine Cells - pathology; Neuroendocrine Tumors - enzymology; Neuroendocrine Tumors - secondary; Neuroendocrine Tumors - urine; Renal Elimination; Stomach Neoplasms - enzymology; Stomach Neoplasms - pathology; Stomach Neoplasms - urine; Urinalysis; Urinary excretion of the main histamine metabolite methylimidazoleacetic acid; Vesicular Monoamine Transport Proteins - analysis; Vesicular monoamine transporter 2; Young Adult
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v21.i47.13240

To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. 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. 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. 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.