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%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >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.

中文翻译：

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泌尿道小细胞神经内分泌癌中胰岛素瘤相关蛋白 1 (INSM1) 的表达

临床指南指出，肌层浸润性膀胱小细胞神经内分泌癌手术前应进行新辅助化疗。据报道，最近描述的标志物胰岛素瘤相关蛋白 1 (INSM1) 对神经内分泌分化具有敏感性和特异性，但是，其在尿路小细胞癌中的疗效尚未确定。本研究检测了尿路小细胞神经内分泌癌全组织切片上 INSM1 的免疫组织化学表达，并将 INSM1 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 CD56、INSM1、突触素和嗜铬粒蛋白的免疫组化染色。对染色强度进行评分（0：无染色；1：弱；2：中等；3：强）和染色的细胞比例（0：0%；1：>0% 至 ≤25%；2：>25% 至 ≤50%；3：>50% 至 ≤75%；4：>75% 至 100 %）。INSM1 在 87% (28/32) 的病例中呈阳性（强度 1 到 3 或比例 1 到 4）（20 例强度 2 到 3，17 例强度 3 到 4）。CD56、突触素和嗜铬粒蛋白分别在 75% (24/32)、60% (19/32) 和 44% (14/32) 的病例中呈阳性。在 34% (11/32) 的病例中，INSM1 为阴性 (n=4) 或仅显示弱强度染色 (n=7)。INSM1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，INSM1 的最佳利用将包含在有限的染色组中，而不是作为独立的筛选标记，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。