Department of Pathology, Fukuoka University School of Medicine.
Department of Neurosurgery, Fukuoka University School of Medicine.
Neurol Med Chir (Tokyo). 2020 Mar 15;60(3):136-146. doi: 10.2176/nmc.oa.2019-0168. Epub 2020 Jan 3.
The histone H3K27M-mutant diffuse midline glioma is often seen in children and has a very poor prognosis regardless of its histological grade. Although it can occur in adults, few studies on adult cases have been reported. We examined adult midline glioma cases for their histological grade, presence of H3K27M mutation, and expression of related factors-enhancer of zeste homolog 2 (EZH2), H3K27me3, p16, and methylthioadenosine phosphorylase. These tumor characteristics were also evaluated for their prognostic value in adult midline glioma. High histological grade, H3K27M-mutant, high EZH2 expression, and high H3K27me3 expression was detected in 12/23 (53%), 11/23 (48%), 9/23 (39%), and 12/23 (52%) cases, respectively. Histological grade and prognosis were significantly correlated (P <0.01). The high expression of EZH2 and the low expression of H3K27me3 correlated with histological malignancy (P = 0.019 and 0.009) and prognosis (P = 0.048 and 0.047). To broaden the scope of our analysis, a review of cases reported in the literature (2014-2019) was performed. In the 171 cases, H3K27M-mutant showed poor prognosis in the young adult group (P = 0.001), whereas H3K27 status had no effect on prognosis in the older age group (P = 0.141). Histological grade was correlated with prognosis in both young adults and older groups (P <0.001, P = 0.003, respectively). We demonstrate differences in prognostic factors for diffuse gliomas in the midline region for children and adults. Importantly, the H3K27M mutation significantly influences prognosis in children, but not necessarily in adults. Contrarily, histological grading and immunostaining are important prognostic tools in adults.
H3K27M 突变弥漫性中线胶质瘤常见于儿童，无论其组织学分级如何，预后均较差。虽然它也可发生于成人，但关于成人病例的研究较少。我们检测了成人中线胶质瘤病例的组织学分级、H3K27M 突变的存在以及相关因素的表达情况，包括增强子结合锌指蛋白 2（EZH2）、H3K27me3、p16 和硫代腺苷磷酸化酶。还评估了这些肿瘤特征在成人中线胶质瘤中的预后价值。在 23 例患者中，分别有 12 例（53%）、11 例（48%）、9 例（39%）和 12 例（52%）检测到高级别组织学、H3K27M 突变、EZH2 高表达和 H3K27me3 高表达。组织学分级和预后有显著相关性（P<0.01）。EZH2 高表达和 H3K27me3 低表达与组织学恶性程度（P=0.019 和 0.009）和预后（P=0.048 和 0.047）相关。为了扩大我们分析的范围，对文献（2014-2019 年）中报道的病例进行了回顾。在 171 例病例中，H3K27M 突变在年轻成年组中预后不良（P=0.001），而 H3K27 状态对老年组的预后没有影响（P=0.141）。组织学分级与年轻成年组和老年组的预后均相关（P<0.001，P=0.003）。我们证明了儿童和成人中线弥漫性胶质瘤的预后因素存在差异。重要的是，H3K27M 突变在儿童中显著影响预后，但在成人中不一定。相反，组织学分级和免疫染色是成人中重要的预后工具。
