Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract
Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract
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DOI：
10.1097/pai.0000000000000824
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发表时间：
2020-10-01
影响因子：
1.6
通讯作者：
Perrino, Carmen M.
中科院分区：
文献类型：
--
作者：
Kim, Isaac E., Jr.;Amin, Ali;Perrino, Carmen M.
临床指南指出，新辅助化疗应在手术前肌肉浸润性膀胱小细胞神经内分泌癌。最近描述的标志物胰岛素瘤相关蛋白1（INSM 1）已被报道是敏感和特异性的神经内分泌分化，然而，其在尿路小细胞癌的疗效还没有很好地建立。本研究检测了泌尿道小细胞神经内分泌癌全组织切片上INSM 1的免疫组化表达，并将INSM 1表达与已建立的神经内分泌标志物进行比较。对32例膀胱小细胞神经内分泌癌进行了CD 56、INSM 1、突触素和嗜铬粒蛋白的免疫组化染色。对染色的强度（0：无染色; 1：弱; 2：中等; 3：强）和染色细胞的比例（0：0%; 1：>0%至25%至50%至75%至100%）进行评分。87%（28/32）的病例（20例为强度2 ~ 3，17例为比例3 ~ 4）INSM 1阳性（强度1 ~ 3或比例1 ~ 4）。CD 56、突触素和嗜铬粒蛋白的阳性率分别为75%（24/32）、60%（19/32）和44%（14/32）。34%（11/32）的病例INSM 1为阴性（n=4）或仅显示弱强度染色（n=7）。INSM 1是泌尿道小细胞神经内分泌分化的敏感标志物。然而，这项研究表明，INSM 1的最佳利用将包括在有限的染色组中，而不是作为一个独立的筛选标记，因为它是阴性的或在很大比例的病例中仅显示弱强度染色。
Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: no staining; 1: weak; 2: moderate; 3: strong) and proportion of cells stained (0: 0%; 1: >0% to 25% to 50% to 75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.