title: Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Apostolos V Tsolakis, Eva T Janson, Section of Endocrine Oncology, Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Apostolos V
authors.initials: AV
authors.lastname: Tsolakis
authors.affiliation: Apostolos V Tsolakis, Eva T Janson, Section of Endocrine Oncology, Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Grimelius
authors.affiliation: Apostolos V Tsolakis, Eva T Janson, Section of Endocrine Oncology, Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Granerus
authors.affiliation: Apostolos V Tsolakis, Eva T Janson, Section of Endocrine Oncology, Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.affiliation: Apostolos V Tsolakis, Eva T Janson, Section of Endocrine Oncology, Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Sture E
authors.initials: SE
authors.lastname: Falkmer
authors.affiliation: Apostolos V Tsolakis, Eva T Janson, Section of Endocrine Oncology, Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Eva T
authors.initials: ET
authors.lastname: Janson
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000556:secondary / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D004759:Enterochromaffin Cells / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D054439:Ghrelin / Q000032:analysis; D006640:Histidine Decarboxylase / Q000032:analysis*; D006801:Humans; D007093:Imidazoles / Q000652:urine*; D008297:Male; D008875:Middle Aged; D055099:Neuroendocrine Cells / Q000201:enzymology* / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000201:enzymology* / Q000556:secondary / Q000652:urine; D065667:Renal Elimination; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000652:urine; D016482:Urinalysis; D050493:Vesicular Monoamine Transport Proteins / Q000032:analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C515349:GHRL protein, human; D054439:Ghrelin; D007093:Imidazoles; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C002667:methylimidazoleacetic acid; D006640:Histidine Decarboxylase
keywords: Enterochromaffin-like cells; Gastric neuroendocrine tumours; High performance liquid chromatography; Histidine decarboxylase; Immunohistochemistry; Urinary excretion of the main histamine metabolite methylimidazoleacetic acid; Vesicular monoamine transporter 2