The expression of NeuroD and mASH1 in the gastroenteropancreatic neuroendocrine tumors
The expression of NeuroD and mASH1 in the gastroenteropancreatic neuroendocrine tumors
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DOI：
10.1038/modpathol.2008.121
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发表时间：
2008-11-01
期刊：
影响因子：
7.5
通讯作者：
Miyazaki, Masaru
中科院分区：
文献类型：
--
作者：
Shida, Takashi;Furuya, Mitsuko;Miyazaki, Masaru
胃肠道胰腺神经内分泌肿瘤是罕见的，其肿瘤生物学至今尚未得到很好的阐明。目前，WHO分类广泛用于诊断和区分这种肿瘤实体，这有时很麻烦。虽然神经内分泌肿瘤标志物确实存在（即嗜铬粒蛋白A，突触蛋白等），但准确预测肿瘤生长和肿瘤行为的敏感和特异性标志物仍然缺乏。在本研究中，我们评估了33例胃肠胰腺神经内分泌肿瘤患者（12例高分化神经内分泌肿瘤，7例高分化神经内分泌癌和14例低分化神经内分泌癌）正常胎儿神经元发育所必需的转录因子（NeuroD和mASH 1）的表达。逆转录-聚合酶链反应显示，与分化良好的神经内分泌肿瘤（类癌）相比，NeuroD在低分化的神经内分泌癌（小细胞型）中表达较少。免疫组化染色显示，mASH 1在低分化神经内分泌癌中高度表达（敏感性为71%），特异性为95%。高NeuroD表达见于所有分化良好的神经内分泌癌和肿瘤（类癌）患者。低分化神经内分泌癌患者中36%（5/14）的NeuroD表达较低，这与总生存期显著缩短相关。这些转录因子的表达模式可能代表了胃肠胰腺神经内分泌肿瘤的生物学和病理生理差异，并可能成为鉴别胃肠胰腺神经内分泌肿瘤的新标志物。
Gastroenteropancreatic neuroendocrine tumors are uncommon and their tumor biology has not been well elucidated to date. Currently the WHO classification is widely used for the diagnosis and distinction of this tumor entity, which is sometimes cumbersome. Although neuroendocrine tumor markers do exist (ie chromograninA, synaptopyhsin, etc), sensitive and specific markers that accurately predict tumor growth and tumor behavior are still absent. In the present study, we assessed the expression of transcription factors (NeuroD and mASH1) essential for the normal fetal neuronal development in 33 gastroenteropancreatic neuroendocrine tumor patients (12 well-differentiated neuroendocrine tumors, 7 well-differentiated neuroendocrine carcinomas, and 14 poorly differentiated neuroendocrine carcinomas). NeuroD was less expressed in poorly differentiated neuroendocrine carcinoma (small-cell type) compared to well-differentiated neuroendocrine tumor (carcinoid) by reverse transcription-polymerase chain reaction. Immunohistochemical staining revealed that mASH1 was highly (sensitivity of 71%) and specifically (specificity of 95%) expressed in poorly differentiated neuroendocrine carcinoma. High NeuroD expression was seen in all well-differentiated neuroendocrine carcinoma and tumor (carcinoid) patients. Low NeuroD expression was seen in 36% (5 of 14) of poorly differentiated neuroendocrine carcinoma patients, which was associated with significant shorter overall survival. The expression pattern of these transcription factors may represent the biological and pathophysiological difference of gastroenteropancreatic neuroendocrine tumors and may become a new marker for the distinction of gastroenteropancreatic neuroendocrine tumors.