Wu Linlin, An Jianduo, Liu Honggang
Department of Pathology, Beijing TongRen Hospital, Capital Medical University, Key Laboratory of Head and Neck Molecular Diagnosis Pathology Beijing, People's Republic of China; Department of Pathology, Beijing LuHe Hospital, Capital Medical University, Beijing, People's Republic of China.
Department of Pathology, Beijing LuHe Hospital, Capital Medical University, Beijing, People's Republic of China.
World Neurosurg. 2022 Mar;159:e23-e31. doi: 10.1016/j.wneu.2021.11.103. Epub 2021 Nov 29.
Because of their rarity, it is not known whether isocitrate dehydrogenase 2 (IDH2) mutations are related to the occurrence of olfactory neuroblastoma (ONB). We investigated the relationships between IDH2 mutations, clinicopathological parameters, and the prognosis for ONB to establish a molecular classification using IDH2 mutations.
An 82-patient cohort was retrospectively screened using immunohistochemistry with a mutation-specific IDH2 antibody and real-time polymerase chain reactions for IDH2 mutations. We also immunohistochemically determined the expression of chromogranin A, synaptophysin, neuron-specific enolase, CD56, S100, and Ki-67.
The 2 methods used for the detection of IDH2 mutations had high consistency. Mutation of IDH2 detected by real-time polymerase chain reaction correlated with higher Kadish stage, Hyams grade, and Ki-67 proliferation index. Mutation of IDH2 correlated negatively with the expression of chromogranin A, synaptophysin, CD56, and S100. Kaplan-Meier analysis showed that an IDH2 mutation, a high Hyams grade, and high Ki-67 proliferation index were associated with poor overall survival. The Hyams grade and IDH2 mutation were independent prognostic factors on multivariable analysis.
Immunohistochemistry was a reliable method to assess the mutation status of IDH2. Tumors with IDH2 mutations represented a distinct subset with aggressive behavior and conferred a poor prognosis. The gene status of IDH2 could be a major molecular classification criterion in ONB.
由于异柠檬酸脱氢酶2（IDH2）突变较为罕见，目前尚不清楚其是否与嗅神经母细胞瘤（ONB）的发生有关。我们研究了IDH2突变、临床病理参数与ONB预后之间的关系，以建立基于IDH2突变的分子分类。
采用针对IDH2突变的特异性抗体进行免疫组织化学和实时聚合酶链反应，对82例患者的队列进行回顾性筛查。我们还通过免疫组织化学方法检测了嗜铬粒蛋白A、突触素、神经元特异性烯醇化酶、CD56、S100和Ki-67的表达。
用于检测IDH2突变的两种方法具有高度一致性。实时聚合酶链反应检测到的IDH2突变与较高的Kadish分期、Hyams分级和Ki-67增殖指数相关。IDH2突变与嗜铬粒蛋白A、突触素、CD56和S100的表达呈负相关。Kaplan-Meier分析显示，IDH2突变、高Hyams分级和高Ki-67增殖指数与总体生存率较差相关。在多变量分析中，Hyams分级和IDH2突变是独立的预后因素。
免疫组织化学是评估IDH2突变状态的可靠方法。具有IDH2突变的肿瘤代表了一个具有侵袭性的独特亚组，预后较差。IDH2的基因状态可能是ONB主要的分子分类标准。
