Jakobsen A M, Andersson P, Saglik G, Andersson E, Kölby L, Erickson J D, Forssell-Aronsson E, Wängberg B, Ahlman H, Nilsson O
Lundberg Laboratory for Cancer Research, University of Göteborg, Sweden.
J Pathol. 2001 Nov;195(4):463-72. doi: 10.1002/path.973.
Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.
神经内分泌肿瘤的特点是具有产生激素的能力，这些激素储存在囊泡和分泌颗粒中。肿瘤中颗粒/囊泡蛋白的显示被视为神经内分泌分化的证据。囊泡单胺转运体（VMAT1和VMAT2）介导胺类进入神经元和内分泌细胞的囊泡。VMAT1和VMAT2的表达以及VMAT1和VMAT2在胃肠道内分泌肿瘤组织病理学诊断中的作用尚未得到充分研究。因此，本研究通过免疫细胞化学和蛋白质印迹法研究了211例人类胃肠道肿瘤中VMAT1和VMAT2的表达。VMAT1和/或VMAT2在大多数起源于胃、回肠和阑尾的胺分泌性内分泌肿瘤中得到证实。产生5-羟色胺的内分泌肿瘤（回肠和阑尾类癌）主要表达VMAT1，而产生组胺的内分泌肿瘤（胃类癌）几乎只表达VMAT2。在产生肽的内分泌肿瘤如直肠类癌和内分泌胰腺肿瘤中，仅观察到少数免疫阳性肿瘤细胞。在非内分泌肿瘤中未发现标记，包括胃、结肠和胰腺腺癌以及胃肠道间质瘤。总之，VMAT1和VMAT2在胃肠道内分泌肿瘤中存在差异表达，每种肿瘤类型具有特定模式，反映了它们的神经内分泌分化和起源。因此，VMAT1和VMAT2可能成为神经内分泌肿瘤分类中有价值的标志物，也可能表明适合通过这些转运系统进行放射性同位素治疗的患者。
