ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin
ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin
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DOI：
10.1038/modpathol.2013.40
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发表时间：
2013-07-01
期刊：
影响因子：
7.5
通讯作者：
Kloeppel, Guenter
中科院分区：
文献类型：
--
作者：
Agaimy, Abbas;Erlenbach-Wuensch, Katharina;Kloeppel, Guenter
人胰岛素基因增强子结合蛋白胰岛-1（ISL 1）是一种参与胰腺神经内分泌细胞分化的转录因子。最近的研究确定ISL 1作为胰腺高分化神经内分泌肿瘤的标志物。然而，很少有人知道在胰腺低分化和胰腺外分化良好和低分化的神经内分泌肿瘤的ISL 1表达。我们研究了124例神经内分泌肿瘤中ISL 1的免疫组化表达。在胰腺神经内分泌肿瘤中，12/13例分化差的肿瘤为阴性，而5/7例分化好但Ki 67>20%的肿瘤为阳性。在胰腺外神经内分泌肿瘤中，默克尔细胞癌（25/25）、肺小细胞神经内分泌癌（21/23）、甲状腺髓样癌（9/9）、副神经节瘤/嗜铬细胞瘤（6/6）、肾上腺神经母细胞瘤（8/8）和头颈部神经内分泌癌（4/5）呈强阳性。而肺类癌（3/15）、嗅神经母细胞瘤（1/4）和基底细胞样头颈部鳞状细胞癌（0/15）无或仅弱染色。ISL 1染色的神经内分泌癌成分的5/8复合癌，也正常的神经内分泌细胞在甲状腺，肾上腺髓质，胃和结直肠。低分化的神经内分泌肿瘤，无论其ISL 1表达，通常是TP 53阳性。我们的研究结果表明，在胰腺外低分化神经内分泌肿瘤和神经母细胞性恶性肿瘤中，ISL 1几乎无处不在表达，而在胰腺低分化神经内分泌肿瘤中，ISL 1的表达普遍缺失。这些研究结果修改了ISL 1作为胰腺神经内分泌肿瘤标志物的作用，并表明ISL 1在神经内分泌肿瘤的分化和生长中的参与比迄今为止所假设的要广泛。
The human insulin gene enhancer-binding protein islet-1 (ISL1) is a transcription factor involved in the differentiation of the neuroendocrine pancreatic cells. Recent studies identified ISL1 as a marker for pancreatic well-differentiated neuroendocrine neoplasms. However, little is known about ISL1 expression in pancreatic poorly differentiated and in extrapancreatic well and poorly differentiated neuroendocrine neoplasms. We studied the immunohistochemical expression of ISL1 in 124 neuroendocrine neoplasms. Among pancreatic neuroendocrine neoplasms, 12/13 with poor differentiation were negative, whereas 5/7 with good differentiation but a Ki67 >20% were positive. In extrapancreatic neuroendocrine neoplasms, strong positivity was found in Merkel cell carcinomas (25/25), pulmonary small cell neuroendocrine carcinomas (21/23), medullary thyroid carcinomas (9/9), paragangliomas/pheochromocytomas (6/6), adrenal neuroblastomas (8/8) and head and neck neuroendocrine carcinomas (4/5), whereas no or only weak staining was recorded in pulmonary carcinoids (3/15), olfactory neuroblastomas (1/4) and basaloid head and neck squamous cell carcinomas (0/15). ISL1 stained the neuroendocrine carcinoma component of 5/8 composite carcinomas and also normal neuroendocrine cells in the thyroid, adrenal medulla, stomach and colorectum. Poorly differentiated neuroendocrine neoplasms, regardless of their ISL1 expression, were usually TP53 positive. Our results show the almost ubiquitous expression of ISL1 in extrapancreatic poorly differentiated neuroendocrine neoplasms and neuroblastic malignancies and its common loss in pancreatic poorly differentiated neuroendocrine neoplasms. These findings modify the role of ISL1 as a marker for pancreatic neuroendocrine neoplasms and suggest that ISL1 has a broader involvement in differentiation and growth of neuroendocrine neoplasms than has so far been assumed.