表达新型神经内分泌标志物胰岛素瘤相关蛋白 1（INSM1）在泌尿生殖系统高级别神经内分泌癌中的研究：免疫组织化学特异性分析，并与嗜铬粒蛋白、突触素和 CD56 的比较。
Expression of novel neuroendocrine marker insulinoma-associated protein 1 (INSM1) in genitourinary high-grade neuroendocrine carcinomas: An immunohistochemical study with specificity analysis and comparison to chromogranin, synaptophysin, and CD56.
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
出版信息
Pathol Res Pract. 2020 Jun;216(6):152993. doi: 10.1016/j.prp.2020.152993. Epub 2020 Apr 26.
Confirmation of genitourinary high-grade neuroendocrine carcinomas (GU-HGNECs) often requires immunohistochemical staining. Here we evaluated a novel neuroendocrine marker, insulinoma-associated protein 1 (INSM1), in GU-HGNECs with comparison to chromogranin, synaptophysin and CD56. Immunohistochemical expression of INSM1, chromogranin, synaptophysin, and CD56 was evaluated in 39 GU-HGNECs using full tissue sections [4 in kidney, 28 in urinary bladder, and 7 in prostate; 31 small cell carcinomas (SmCCs), 6 large cell neuroendocrine carcinomas (LCNECs), 2 mixed SmCC-LCNECs]. In 33 SmCCs/components, INSM1 showed similar sensitivity (93.9 %) to chromogranin (87.8 %), synaptophysin (93.9 %) and CD56 (87.8 %), and stained a similar percentage of tumor cells (52 %) to chromogranin (49 %) and CD56 (52 %), but lower than synaptophysin (87 %) (p < 0.0001). In 8 LCNECs/components, INSM1 is similar to chromogranin, synaptophysin or CD56 in sensitivity (62.5 %, 62.5 %, 75 %, 62.5 %, respectively) and the mean percentage of positively stained tumor cells (21 %, 44 %, 48 %, 37 %, respectively). INSM1 is more sensitive for SmCCs than LCNECs (93.9 % vs. 62.5 %, p = 0.015). INSM1 showed 97.4 % specificity upon analyzing 273 genitourinary non-neuroendocrine tumors on tissue microarrays. Our study indicates that INSM1 is a sensitive marker for genitourinary HGNECs with high specificity. For genitourinary SmCCs, INSM1 shows similar sensitivity to chromogranin, synaptophysin and CD56 but stains a lower percentage of tumor cells than synaptophysin. For genitourinary LCNECs, INSM1 showed similar sensitivity to chromogranin, synaptophysin and CD56. INSM1 is more sensitive for genitourinary SmCCs than LCNECs. Our result and literature review indicate that whether INSM1 is more sensitive than conventional neuroendocrine markers for HGNECs depends on the tumor primary sites.
泌尿系统高级别神经内分泌癌（GU-HGNEC）的确诊通常需要免疫组织化学染色。在此，我们评估了一种新的神经内分泌标志物胰岛素瘤相关蛋白 1（INSM1），并与嗜铬粒蛋白、突触素和 CD56 进行了比较。使用全组织切片评估了 39 例 GU-HGNEC 中 INSM1、嗜铬粒蛋白、突触素和 CD56 的免疫组织化学表达[肾脏 4 例，膀胱 28 例，前列腺 7 例；31 例小细胞癌（SmCC），6 例大细胞神经内分泌癌（LCNEC），2 例 SmCC-LCNEC 混合]。在 33 例 SmCC 成分中，INSM1 对嗜铬粒蛋白（87.8%）、突触素（93.9%）和 CD56（87.8%）的敏感性与嗜铬粒蛋白相似，染色的肿瘤细胞百分比也相似（52%对嗜铬粒蛋白为 49%，对 CD56 为 52%），但低于突触素（87%）（p<0.0001）。在 8 例 LCNEC 成分中，INSM1 的敏感性与嗜铬粒蛋白、突触素或 CD56 相似（62.5%、62.5%、75%、62.5%），阳性染色肿瘤细胞的平均百分比（21%、44%、48%、37%）也相似。INSM1 对 SmCC 的敏感性高于 LCNEC（93.9%比 62.5%，p=0.015）。在分析组织微阵列上的 273 例泌尿生殖系统非神经内分泌肿瘤时，INSM1 的特异性为 97.4%。我们的研究表明，INSM1 是一种具有高特异性的泌尿生殖系统 HGNEC 敏感标志物。对于泌尿生殖系统 SmCC，INSM1 对嗜铬粒蛋白、突触素和 CD56 的敏感性与嗜铬粒蛋白相似，但染色的肿瘤细胞百分比低于突触素。对于泌尿生殖系统 LCNEC，INSM1 对嗜铬粒蛋白、突触素和 CD56 的敏感性与嗜铬粒蛋白相似。INSM1 对泌尿生殖系统 SmCC 的敏感性高于 LCNEC。我们的结果和文献综述表明，INSM1 是否比传统神经内分泌标志物对 HGNEC 更敏感取决于肿瘤的原发部位。
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