Wang Hannah, Krishnan Chandra, Charville Gregory W
Department of Pathology, Stanford University School of Medicine, Stanford, California.
Stanford Hospital and Clinics, Stanford, California.
Pediatr Dev Pathol. 2019 Oct;22(5):440-448. doi: 10.1177/1093526619843725. Epub 2019 Apr 11.
Insulinoma-associated protein 1 (INSM1) is a transcription factor that functions in neuroepithelial tissue development and shows expression in neuroendocrine neoplasms. Given the role of INSM1 in controlling differentiation of the sympatho-adrenal lineage, we hypothesized that INSM1 expression would define a subset of neuroblastic tumors. This study aimed to characterize the immunohistochemical profile of INSM1 in a cohort of peripheral neuroblastic tumors and compare INSM1 expression in these tumors to that seen in other embryonal neoplasms, using both tissue microarrays and whole-slide histologic sections. INSM1 showed nuclear expression in 39/50 (78%) peripheral neuroblastic tumors, including 27/32 (84%) neuroblastomas, 9/9 (100%) ganglioneuroblastomas, and 3/9 (33%) ganglioneuromas. Altogether, 70% of peripheral neuroblastic tumors showed anti-INSM1 immunoreactivity in more than 20% of tumor nuclei. Although no non-neuroblastic tumors in this study exhibited INSM1 expression in more than 20% of nuclei, focal or patchy staining was identified in 7/14 (50%) rhabdomyosarcomas, 7/22 (32%) nephroblastomas, and 4/20 (20%) Ewing sarcomas. The absence of INSM1 expression in peripheral neuroblastic tumors was restricted to undifferentiated and poorly differentiated neuroblastomas, as well as mature ganglioneuromas, mimicking the transient INSM1 expression seen in sympatho-adrenal differentiation during normal development. No significant association between amplification status and INSM1 expression was observed. We found that all 3 INSM1-negative neuroblastoma patients with available follow-up were alive at a median of 15 years, in comparison to 9 of 13 INSM1-positive neuroblastoma patients living at a median of 5 years. Additional studies are needed to determine whether INSM1 expression is indicative of a clinically significant differentiation state in neuroblastoma.
胰岛素瘤相关蛋白1（INSM1）是一种转录因子，在神经上皮组织发育中发挥作用，并在神经内分泌肿瘤中表达。鉴于INSM1在控制交感-肾上腺谱系分化中的作用，我们推测INSM1表达可定义成神经母细胞瘤的一个亚群。本研究旨在通过组织芯片和全切片组织学切片，描述一组外周神经母细胞瘤中INSM1的免疫组化特征，并比较这些肿瘤中INSM1的表达与其他胚胎性肿瘤中的表达情况。INSM1在50例外周神经母细胞瘤中的39例（78%）呈核表达，包括32例神经母细胞瘤中的27例（84%）、9例节细胞神经母细胞瘤中的9例（100%）和9例神经节瘤中的3例（33%）。总计，70%的外周神经母细胞瘤在超过20%的肿瘤细胞核中显示抗INSM1免疫反应性。虽然本研究中没有非神经母细胞瘤在超过20%的细胞核中表现出INSM1表达，但在14例横纹肌肉瘤中的7例（50%）、22例肾母细胞瘤中的7例（32%）和20例尤因肉瘤中的4例（20%）中发现了局灶性或斑片状染色。外周神经母细胞瘤中INSM1表达的缺失仅限于未分化和低分化神经母细胞瘤以及成熟神经节瘤，这与正常发育过程中交感-肾上腺分化时短暂的INSM1表达相似。未观察到扩增状态与INSM1表达之间存在显著关联。我们发现，所有3例有随访信息的INSM1阴性神经母细胞瘤患者均存活，中位生存期为15年，相比之下，13例INSM1阳性神经母细胞瘤患者中有9例存活，中位生存期为5年。需要进一步研究以确定INSM1表达是否指示神经母细胞瘤中具有临床意义的分化状态。
