Tumors of the central nervous system (CNS) in pediatric patients have undergone significant diagnostic refinement through the use of immunohistochemistry (IHC) and molecular techniques. The utility of these novel IHC antibodies has been demonstrated with the inactivation of the switch/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in the diagnosis of atypical teratoid/rhabdoid tumors, predominantly through the loss of integrase interactor 1 (INI1; SMARCB1). Alternatively, these tumors may have inactivation of brahma-related gene 1 (BRG1; SMARCA4) in a subset of cases. The role of other SWI/SNF component proteins and their expression in pediatric brain tumors is not well established. Nestin, an intermediate filament, has been shown to be present in some pediatric CNS tumors, but of uncertain diagnostic and prognostic significance. We sought to explore the immunohistochemical expression profile for common SWI/SNF subunits and nestin in a pediatric CNS tumor cohort. Using a 118-sample tissue microarray, we performed IHC for INI1, BRG1, brahma (BRM), ARID1A, ARID1B, polybromo 1, and nestin. In 19 cases, INI1 was lost and BRG1 was lost in 2 cases. Interestingly, 6 cases originally diagnosed as primitive neuroectodermal tumors showed isolated loss of BRM. Other SWI/SNF proteins did not provide further diagnostic resolution. Nestin was positive in 76.2% of INI1/BRG1-deficient tumors, compared with 29.1% in INI1/BRG1-intact tumors yielding a sensitivity of 76.2%, specificity of 68.0%, and a P value of <0.001, but nestin positivity did not correlate specifically with poor outcomes. In conclusion, we confirm the utility of BRG1 IHC in the workup of pediatric CNS tumors, which may facilitate a difficult diagnosis when conventional markers are inconclusive, or as a first-line marker in cases where intraoperative smears are suggestive of atypical teratoid/rhabdoid tumor. Although nestin expression was associated with SWI/SNF inactivation, it did not yield statistically significant diagnostic or prognostic information in our study. Interestingly, we identified 6 tumors with isolated BRM IHC loss, the significance of which is uncertain but warrants further investigation.

通过使用免疫组织化学 (IHC) 和分子技术，儿科患者的中枢神经系统 (CNS) 肿瘤的诊断得到了显着的改进。这些新型 IHC 抗体的实用性已通过开关/蔗糖非发酵 (SWI/SNF) 染色质重塑复合物的失活在非典型畸胎瘤/横纹肌样肿瘤的诊断中得到证实，主要是通过整合酶相互作用蛋白 1 (INI1; SMARCB1 ) 的缺失）。或者，在部分病例中，这些肿瘤可能存在 Brahma 相关基因 1（BRG1；SMARCA4 ）失活。其他 SWI/SNF 成分蛋白的作用及其在儿童脑肿瘤中的表达尚未明确。巢蛋白是一种中间丝，已被证明存在于一些儿科中枢神经系统肿瘤中，但其诊断和预后意义尚不确定。我们试图探索儿科中枢神经系统肿瘤队列中常见 SWI/SNF 亚基和巢蛋白的免疫组织化学表达谱。使用 118 个样本的组织微阵列，我们对 INI1、BRG1、brahma (BRM)、ARID1A、ARID1B、多溴 1 和巢蛋白进行 IHC 。19例INI1丢失， 2例BRG1丢失。有趣的是，6 例最初诊断为原始神经外胚层肿瘤的病例显示出 BRM 的孤立缺失。其他 SWI/SNF 蛋白未提供进一步的诊断分辨率。76.2% 的 INI1/ BRG1缺陷型肿瘤中巢蛋白呈阳性，而 INI1/ BRG1完整肿瘤中巢蛋白阳性率为 29.1%，敏感性为 76.2%，特异性为 68.0%，P值 <0.001，但巢蛋白阳性率并未升高。与不良结果特别相关。总之，我们证实了BRG1 IHC 在儿童中枢神经系统肿瘤检查中的实用性，当传统标记物不确定时，这可能有助于诊断困难，或者在术中涂片提示非典型畸胎瘤/横纹肌样瘤的情况下作为一线标记物。尽管巢蛋白表达与 SWI/SNF 失活相关，但在我们的研究中它并未产生具有统计学意义的诊断或预后信息。有趣的是，我们发现 6 个肿瘤存在孤立的 BRM IHC 缺失，其意义尚不确定，但值得进一步研究。