Department of Pathology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
22494Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Int J Surg Pathol. 2021 Sep;29(6):615-626. doi: 10.1177/1066896921995935. Epub 2021 Mar 2.
Insulinoma-associated protein 1 (INSM1) is shown to be an excellent marker for neuroendocrine differentiation. However, the diagnostic utility of INSM1 in medullary thyroid carcinoma (MTC) has not yet been extensively investigated. INSM1 staining was performed on 21 MTCs, 7 MTC mimickers (including 3 papillary carcinomas, 2 poorly differentiated carcinomas, 1 follicular adenoma, and 1 nodular plasma cell hyperplasia), and 3 cases of C-cell hyperplasia. INSM1 staining of these cases was compared with the traditional MTC markers including calcitonin (CT), monoclonal carcinoembryonic antigen (mCEA), chromogranin A (CgA), and synaptophysin (Syn). The -score was generated using the QuPath program, an open-source image analysis software. All 21 MTC cases and 3 C-cell hyperplasia cases were positive for all markers. The MTC mimickers were entirely negative for INSM1. INSM1 and Syn displayed, more consistently, high expression with minimal variability than CgA that showed a wide range of expression with significant variability. mCEA and CT exhibited mostly a high expression with some variability. Being a nuclear stain, interpretation was easier with INSM1 compared to other cytoplasmic markers. INSM1 is an excellent marker for neuroendocrine differentiation, entirely applicable in the diagnosis of MTC and C-cell hyperplasia with high sensitivity and specificity. In comparison with the traditional MTC markers, INSM1 is unique in the crisp nuclear staining pattern with a consistent, diffuse, and strong expression. INSM1 can be potentially combined with CT or mCEA as a dual stain, especially when the lesional tissue is limited for a panel of immunostains.
胰岛素瘤相关蛋白 1（INSM1）被证明是神经内分泌分化的极佳标志物。然而，INSM1 在甲状腺髓样癌（MTC）中的诊断效用尚未得到广泛研究。对 21 例 MTC、7 例 MTC 模拟物（包括 3 例乳头状癌、2 例低分化癌、1 例滤泡性腺瘤和 1 例结节性浆细胞增生）和 3 例 C 细胞增生进行了 INSM1 染色。将这些病例的 INSM1 染色与传统的 MTC 标志物包括降钙素（CT）、单克隆癌胚抗原（mCEA）、嗜铬粒蛋白 A（CgA）和突触素（Syn）进行了比较。使用 QuPath 程序（一种开源图像分析软件）生成了 -score。所有 21 例 MTC 病例和 3 例 C 细胞增生病例均对所有标志物呈阳性。MTC 模拟物完全不表达 INSM1。INSM1 和 Syn 的表达一致性更高，变异性更小，而 CgA 的表达范围更广，变异性更大。mCEA 和 CT 主要表现为高表达，变异性较小。与其他细胞质标志物相比，INSM1 作为核染色，解释起来更容易。INSM1 是神经内分泌分化的极佳标志物，完全适用于 MTC 和 C 细胞增生的诊断，具有高灵敏度和特异性。与传统的 MTC 标志物相比，INSM1 的独特之处在于其清晰的核染色模式，具有一致、弥漫和强烈的表达。INSM1 可以与 CT 或 mCEA 联合作为双重染色，尤其是在病变组织有限时，需要进行免疫组化组合染色。
