Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin.
Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin.
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DOI：
10.1007/s12022-020-09645-y
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发表时间：
2020-12
影响因子：
4.4
通讯作者：
Höög A
中科院分区：
文献类型：
--
作者：
Juhlin CC;Zedenius J;Höög A
神经内分泌肿瘤（NENs）传统上是通过与分泌囊泡和颗粒调节相关的蛋白质表达来鉴定的。我们报道了“第二代”蛋白ISL LIM homobox 1 （ISL1）、INSM转录抑制因子1 （INSM1）和分泌素（SECG）作为神经内分泌分化的免疫组织化学标志物的临床应用，并将结果与已建立的蛋白chromogranin A （CGA）和synaptophysin （SYP）进行了比较。总共有161个肿瘤，包括139个NEN和22个“非NENs”（最初怀疑为NEN的不相关肿瘤），进行了ISL1的信息染色，并对亚群进行了INSM1和/或SECG的检测。在91/139名nen患者中ISL1（65%）和6/22名非nen患者中（27%）出现弥漫性或局灶性阳性免疫反应，在76/85名nen患者中INSM1（89%）和2/5名非nen患者中（40%）出现免疫反应，在64名nen患者中有49名SECG（77%）和0/5名非nen患者中（0%）出现免疫反应。一般来说，ISL1、INSM1和SECG的敏感性与CGA和syp相当或略低于CGA和syp，这主要归因于肿瘤起源的组织特异性模式。此外，对于胰腺和小肠NENs这两个最大的亚组，无论肿瘤来源和WHO分级如何，ISL1染色结果都是一致的。我们验证了先前建议的第一代和第二代神经内分泌标记物的免疫组织化学方案，以促进NENs的诊断过程，并确认第二代神经内分泌标记物显示组织特异性模式。因此，我们建议在三级内分泌病理中心实施，尤其是在分析转移时帮助鉴定原发肿瘤。本文的在线版本（10.1007/s12022-020-09645-y）包含补充资料，仅供授权用户使用。
Neuroendocrine neoplasms (NENs) have traditionally been identified via expression of proteins associated to the regulation of secretory vesicles and granules. We report the clinical usage of the “second-generation” proteins ISL LIM homeobox 1 (ISL1), INSM transcriptional repressor 1 (INSM1), and secretagogin (SECG) as immunohistochemical markers of neuroendocrine differentiation since their introduction in clinical routine and compare the results with the established proteins chromogranin A (CGA) and synaptophysin (SYP). In total, 161 tumors, including 139 NENs and 22 “non-NENs” (unrelated tumors with an initial suspicion of NEN), were informatively stained for ISL1, and subsets were also interrogated for INSM1 and/or SECG. Diffuse or focal positive immunoreactivity was noted for ISL1 in 91/139 NENs (65%) and in 6/22 (27%) non-NENs, for INSM1 in 76/85 NENs (89%) and in 2/5 (40%) non-NENs, and for SECG in 49 out of 64 NENs (77%) and in 0/5 non-NENs (0%). Generally, ISL1, INSM1, and SECG exhibited sensitivities in line with or slightly below that of CGA and SYP—largely attributable to tissue-specific patterns regarding tumoral origin. Moreover, for pancreatic and small intestinal NENs, the two largest subgroups, ISL1 staining results were consistent irrespectively of tumor source and WHO grade. We verify previously suggested immunohistochemical schemes of neuroendocrine markers of first- and second-generations to facilitate the diagnostic process for NENs and confirm that the second-generation neuroendocrine markers display tissue-specific patterns. We therefore recommend their implementation in tertiary endocrine pathology centers, not least to aid in the identification of primary tumors when analyzing metastases. The online version of this article (10.1007/s12022-020-09645-y) contains supplementary material, which is available to authorized users.
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