Importance of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors.
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.
Nilsson
Ola
O
Lundberg Laboratory for Cancer Research at the Departments of Pathology, Radiation Physics and Surgery, Sahlgrenska University Hospital, Göteborg, Sweden. ola.nilsson@llcr.med.gu.se
Jakobsen
Anne-Marie Levin
AM
Kölby
Lars
L
Bernhardt
Peter
P
Forssell-Aronsson
Eva
E
Ahlman
Håkan
H
D019797:3-Iodobenzylguanidine / Q000378:metabolism / Q000494:pharmacology; D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D000310:Adrenal Gland Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D001706:Biopsy; D002276:Carcinoid Tumor / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D002864:Chromogranins; D002997:Clomipramine / Q000494:pharmacology; D019205:GTP-Binding Protein alpha Subunits, Gs; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D009479:Neuropeptides; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D010673:Pheochromocytoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D011877:Radionuclide Imaging; D012110:Reserpine / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000378:metabolism; D014407:Tumor Cells, Cultured; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D019797:3-Iodobenzylguanidine; D018759:Adrenergic Uptake Inhibitors; D002864:Chromogranins; D002997:Clomipramine; D019205:GTP-Binding Protein alpha Subunits, Gs; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012110:Reserpine; D017367:Selective Serotonin Reuptake Inhibitors; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C493449:SLC18A1 protein, human; C076414:SV2A protein, human; C406732:GNAS protein, human