Rocha Maria Linda, Schmid Kurt Werner, Czapiewski Piotr
Institute of Pathology Königs Wusterhausen, Königs Wusterhausen, Germany.
Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Contemp Oncol (Pozn). 2021;25(3):213-223. doi: 10.5114/wo.2021.110052. Epub 2021 Oct 14.
Anaplastic thyroid carcinoma is a rare, rapidly progressing, highly aggressive thyroid malignancy. Responses to immune checkpoint inhibitors in mismatch repair-deficient/microsatellite instability-high tumours of other locations have shown promising results, and with the extended approval of the PD-1 receptor inhibitor pembrolizumab by the Food and Drug Administration, also anaplastic thyroid cancer (ATC) requires analysis for microsatellite instability (MSI) status.
Systematic research for relevant literature was conducted in different databases. Prevalence, detection methods, and the potential prognostic/predictive value of MSI in view of the available targeted therapies were of special focus.
Selected citations revealed the prevalence of MSI in 7.4%, with mutations in the MSH2 gene (33%) being the most frequent, followed by MSH6 (25%) and MLH1 (16.7%) occurring in the following combinations: MLH1-MSH2 (8.3%), MSH2-MSH6 (8.3%), and MLH3-MSH5 (8.3%). No mutations in the PMS2 gene were reported. Sixty-six co-mutations in 9 cases were found, with TP53 (88.9%), NF1 (44.4 %), ATM (33.3%), and RB1 (33.3%) being the most frequent. No RAS mutations were noted. Survival ranged between 2.8 and 48 months, and patient age varied between 49 and 84 years. There are insufficient and heterogenous data concerning the predictive or prognostic value of mismatch repair-deficient/microsatellite instability status.
Tumour molecular profiling is fundamental in ATC for predictive, prognostic, as well as therapeutic reasons, and analysis of MSI status is strongly suggested because a small subgroup show the MSI signature and might profit from recently approved targeted therapies.
间变性甲状腺癌是一种罕见的、进展迅速、侵袭性很强的甲状腺恶性肿瘤。在其他部位错配修复缺陷/微卫星高度不稳定的肿瘤中，免疫检查点抑制剂的治疗反应已显示出有前景的结果，随着美国食品药品监督管理局对程序性死亡受体1（PD-1）受体抑制剂帕博利珠单抗的扩大批准，间变性甲状腺癌（ATC）也需要分析微卫星不稳定性（MSI）状态。
在不同数据库中对相关文献进行系统检索。特别关注MSI的患病率、检测方法以及鉴于现有靶向治疗其潜在的预后/预测价值。
所选文献显示MSI的患病率为7.4%，其中错配修复蛋白2（MSH2）基因的突变最为常见（33%），其次是错配修复蛋白6（MSH6）（25%）和错配修复蛋白1（MLH1）（16.7%），它们以以下组合形式出现：MLH1-MSH2（8.3%）、MSH2-MSH6（8.3%）和错配修复蛋白三（MLH3）-错配修复蛋白五（MSH5）（8.3%）。未报告错配修复蛋白二（PMS2）基因的突变。在9例患者中发现了66个共突变，其中最常见的是肿瘤蛋白p53（TP53）（88.9%）、神经纤维瘤蛋白1（NF1）（44.4%）、共济失调毛细血管扩张症突变基因（ATM）（33.3%）和视网膜母细胞瘤蛋白（RB1）（33.3%）。未发现RAS突变。生存期在2.8至48个月之间，患者年龄在49至84岁之间。关于错配修复缺陷/微卫星不稳定性状态的预测或预后价值，数据不足且存在异质性。
出于预测、预后以及治疗方面的原因，肿瘤分子谱分析在ATC中至关重要，强烈建议分析MSI状态，因为一小部分亚组显示出MSI特征，可能会从最近批准的靶向治疗中获益。
