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Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors.

Journal article
Authors Lars Kölby
Bo Wängberg
Håkan Ahlman
Svante Jansson
Eva Forssell-Aronsson
J D Erickson
O Nilsson
Published in Digestion
Volume 59
Issue 2
Pages 160-6
ISSN 0012-2823
Publication year 1998
Published at Institute of Selected Clinical Sciences, Department of Radiation Physics
Institute of Surgical Sciences, Department of Surgery
Pages 160-6
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Aged, Biological Transport, genetics, Blotting, Northern, Carcinoid Tumor, metabolism, pathology, ultrastructure, Female, Gene Expression, genetics, Histamine, analysis, biosynthesis, Humans, Immunohistochemistry, Membrane Glycoproteins, genetics, Membrane Transport Proteins, Neuropeptides, Neurotransmitter Agents, genetics, RNA, Messenger, analysis, genetics, Receptors, Histamine, analysis, biosynthesis, Receptors, Somatostatin, genetics, Stomach Neoplasms, chemistry, metabolism, pathology, Tumor Cells, Cultured, Vesicular Biogenic Amine Transport Proteins, Vesicular Monoamine Transport Proteins
Subject categories Cancer and Oncology, Gastroenterology and Hepatology

Abstract

A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MelmAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.

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