Abstract
We have analyzed the expression of synaptic vesicle proteins in human neuroendocrine tumors and the potential use of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. Biopsies from endocrine and nonendocrine tumors of the gastrointestinal tract, pancreas, and adrenals were examined by immunocytochemistry using antibodies against synaptic vesicle protein 2 (SV2), vesicular monoamine transporter 1 and 2 (VMAT1 and 2), and neuroendocrine secretory protein 55 (NESP55). SV2 was expressed in all endocrine tumors of the gastrointestinal tract and pancreas as well as in gastrointestinal stromal tumors (GISTs). None of the adenocarcinomas expressed SV2. VMAT1 and 2 were expressed in amine-producing tumors of the gastrointestinal tract (ECL cell and EC cell carcinoids) and in a small number of peptide-producing pancreatic endocrine tumors. NESP55 was expressed in neuroblastomas and adrenal pheochromocytomas as well as in a subgroup of pancreatic endocrine tumors. The importance of VMAT1 and 2 for the uptake of 123I-MIBG in tumor cells was demonstrated. It was concluded that neuroendocrine tumors express multiple synaptic vesicle proteins that are useful in the histopathological diagnosis and classification of tumors. Vesicle proteins may prove to be useful for targeting tumor therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Iodobenzylguanidine / metabolism
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3-Iodobenzylguanidine / pharmacology
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Adenocarcinoma / diagnostic imaging
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Adenocarcinoma / pathology
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Adenocarcinoma / therapy
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Adrenal Gland Neoplasms / diagnostic imaging
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Adrenal Gland Neoplasms / pathology
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Adrenal Gland Neoplasms / therapy
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Adrenergic Uptake Inhibitors / pharmacology
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Biopsy
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Carcinoid Tumor / diagnostic imaging
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Carcinoid Tumor / pathology
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Carcinoid Tumor / therapy
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Chromogranins
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Clomipramine / pharmacology
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GTP-Binding Protein alpha Subunits, Gs*
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Gastrointestinal Neoplasms / diagnostic imaging
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Gastrointestinal Neoplasms / pathology*
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Gastrointestinal Neoplasms / therapy*
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Humans
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Iodine Radioisotopes
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Membrane Glycoproteins / metabolism*
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Membrane Transport Proteins*
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Nerve Tissue Proteins / metabolism*
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Neuroblastoma / diagnostic imaging
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Neuroblastoma / pathology
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Neuroblastoma / therapy
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Neuroendocrine Tumors / diagnostic imaging
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Neuroendocrine Tumors / pathology*
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Neuroendocrine Tumors / therapy*
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Neuropeptides*
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Pancreatic Neoplasms / diagnostic imaging
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / therapy
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Pheochromocytoma / diagnostic imaging
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Pheochromocytoma / pathology
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Pheochromocytoma / therapy
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Radionuclide Imaging
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Reserpine / pharmacology
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Synaptic Vesicles / metabolism
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Tumor Cells, Cultured
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Vesicular Biogenic Amine Transport Proteins
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Vesicular Monoamine Transport Proteins
Substances
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Adrenergic Uptake Inhibitors
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Chromogranins
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Iodine Radioisotopes
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Neuropeptides
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SLC18A1 protein, human
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Serotonin Uptake Inhibitors
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Vesicular Biogenic Amine Transport Proteins
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Vesicular Monoamine Transport Proteins
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SV2A protein, human
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3-Iodobenzylguanidine
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Reserpine
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GNAS protein, human
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GTP-Binding Protein alpha Subunits, Gs
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Clomipramine