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Abstract：
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.
摘要：
泌尿生殖系统高级别神经内分泌癌（GU-HGNEC）的确认通常需要免疫组织化学染色。在这里，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），在GU-HGNEC中，与嗜铬粒蛋白相比，突触素和CD56。免疫组织化学表达的INSM1，嗜铬粒蛋白，突触素,和CD56在39个GU-HGNECs中使用全组织切片[4在肾脏中，28膀胱，前列腺7例；31例小细胞癌（SmCC），6大细胞神经内分泌癌（LCNECs），2个混合SmCC-LCNECs]。在33个SmCC/组件中，INSM1显示与嗜铬粒蛋白（87.8%）相似的敏感性（93.9%），突触素（93.9%）和CD56（87.8%），和染色相似百分比的肿瘤细胞（52％）与嗜铬粒蛋白（49％）和CD56（52％），但低于突触素(87%)(p<0.0001)。在8个LCNEC/组件中，INSM1类似于嗜铬粒蛋白，突触素或CD56的敏感性（62.5%，62.5%,75%,62.5%,分别）和阳性染色肿瘤细胞的平均百分比（21%，44%,48%,37%,分别)。INSM1对SmCC比LCNEC更敏感（93.9%与62.5%,p=0.015)。在组织微阵列上分析273例泌尿生殖系统非神经内分泌肿瘤后，INSM1显示出97.4％的特异性。我们的研究表明，INSM1是泌尿生殖系统HGNECs的敏感标记，具有很高的特异性。对于泌尿生殖系统SmCC，INSM1对嗜铬粒蛋白有相似的敏感性,突触素和CD56，但对肿瘤细胞的染色百分比低于突触素。对于泌尿生殖系统LCNEC，INSM1对嗜铬粒蛋白有相似的敏感性,突触素和CD56。INSM1对泌尿生殖系统SmCC比LCNEC更敏感。我们的结果和文献综述表明，INSM1是否比HGNECs的常规神经内分泌标志物更敏感取决于肿瘤的原发部位。
