Kim Sujeong, Seo Jisu, Shin Youjung, Kim Moonsik
School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, 41405, Republic of Korea.
Discov Oncol. 2025 May 13;16(1):754. doi: 10.1007/s12672-025-02576-2.
Insulinoma-associated protein 1 (INSM1) is a recently added nuclear marker for neuroendocrine differentiation. However, INSM1 expression in gastric neuroendocrine and non-neuroendocrine neoplasms has not been thoroughly investigated.
We examined INSM1 expression in 72 gastric tumors, including 22 gastric neuroendocrine tumors and 50 gastric non-neuroendocrine neoplasms. Synaptophysin and chromogranin immunostaining were also performed for all cases.
For gastric neuroendocrine neoplasms, INSM1 immunostaining demonstrated excellent sensitivity (21/22, 95.5%), comparable to synaptophysin (22/22, 100.0%), but had lower specificity (32/50, 64.0%) compared with traditional neuroendocrine markers (synaptophysin (36/50, 72.0%) and chromogranin (42/50, 84.0%)). However, decreased expression of INSM1, measured by H-score, was frequently found among neuroendocrine carcinoma cases. Gastric non-neuroendocrine neoplasms frequently exhibited INSM1 positivity (18/50, 36.0%); however, in most cases (16/18, 88.9%), staining was focal (involving < 10% of tumor cells). Tumor histologic subtype and grade may be associated with INSM1 expression.
INSM1 nuclear positivity in gastric neoplasms should be interpreted with caution. INSM1 should not be used as a stand-alone marker for determining neuroendocrine differentiation in gastric tumors. Histologic evaluation with concurrent use of traditional neuroendocrine markers is warranted to accurately demonstrate neuroendocrine differentiation and minimize false positivity and false negativity.
胰岛素瘤相关蛋白1（INSM1）是最近添加的用于神经内分泌分化的核标志物。然而，INSM1在胃神经内分泌和非神经内分泌肿瘤中的表达尚未得到充分研究。
我们检测了72例胃肿瘤中INSM1的表达，其中包括22例胃神经内分泌肿瘤和50例胃非神经内分泌肿瘤。所有病例均进行了突触素和嗜铬粒蛋白免疫染色。
对于胃神经内分泌肿瘤，INSM1免疫染色显示出极佳的敏感性（21/22，95.5%），与突触素（22/22，100.0%）相当，但与传统神经内分泌标志物（突触素（36/50，72.0%）和嗜铬粒蛋白（42/50，84.0%））相比，特异性较低（32/50，64.0%）。然而，通过H评分测量发现，神经内分泌癌病例中INSM1表达常降低。胃非神经内分泌肿瘤常表现出INSM1阳性（18/50，36.0%）；然而，在大多数病例（16/18，88.9%）中，染色为局灶性（累及<10%的肿瘤细胞）。肿瘤组织学亚型和分级可能与INSM1表达有关。
胃肿瘤中INSM1核阳性的解读应谨慎。INSM1不应作为确定胃肿瘤神经内分泌分化的独立标志物。同时使用传统神经内分泌标志物进行组织学评估，以准确显示神经内分泌分化并尽量减少假阳性和假阴性是必要的。
