Purpose

H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages.

Methods

One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed.

Results

DMGs comprised 5.3% of all gliomas with 49.2% H3K27M mutant and 50.8% wild types. Majority (75.68%) of pediatric and 38.20% of adults were H3K27M mutant (p = 0.0001). Amongst H3K27M mutants, brainstem (46.43%) was the commonest location in pediatric and thalamus (61.76%) in adults. H3K27M mutation was mutually exclusive with IDH mutation in 93.55%, while p53, ATRX mutation were seen in 56.4% and 30.6% cases respectively. Software-based immunohistochemistry evaluation (H-scoring) showed 99.2% concordance with sequencing for H3K27M mutation. Radiologically, no significant difference in contrast enhancement was seen between mutant and wild types (p = 0.05). The difference in overall survival (OS) was not significant in mutant versus wild types, with age or location. Tumor resection independently and on correlation with H3K27M did not influence OS (p = 0.51 and p = 0.47). Adjuvant therapy impacted survival significantly in adults (p = 0.0009), however, not in pediatric cases (p = 0.06).

Conclusions

The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.

中文翻译：

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弥漫性中线神经胶质瘤的临床病理和分子特征：是否具有预后意义？

目的

H3K27M突变型弥漫性中线神经胶质瘤（DMG）被认为是IV级，而与组织学特征无关，预后不良。我们评估了所有年龄段的DMG的临床病理，放射学和分子特征。

方法

在过去的10年中，共发现了26个DMG。对H3K27M，ATRX，IDH1和p53进行了免疫组织化学，对IDH1和H3K27M突变进行了Sanger测序。回顾了患者的人口统计学和临床​​放射学特征，并进行了生存分析。

结果

DMG占所有神经胶质瘤的5.3％，其中H3K27M突变体为49.2％，野生型为50.8％。绝大多数（75.68％）的儿科患者和38.20％的成年人是H3K27M突变体（p  = 0.0001）。在H3K27M突变体中，成人的脑干（46.43％）是小儿和丘脑中最常见的位置（61.76％）。H3K27M突变与IDH突变互斥，占93.55％，而p53，ATRX突变分别占56.4％和30.6％。基于软件的免疫组化评估（H评分）显示H3K27M突变与测序的一致性为99.2％。放射学上，突变型和野生型之间对比度增强没有显着差异（p = 0.05）。突变体与野生型的总生存期（OS）的差异不随年龄或地理位置而变化。单独进行肿瘤切除以及与H3K27M的相关性均不影响OS（p  = 0.51和p  = 0.47）。辅助治疗显着影响成年人的存活率（p  = 0.0009），而在儿科病例中则没有（p  = 0.06）。

结论

这项研究突出了儿科和成人DMG的频率和位置的差异。H3K27M突变的IHC（H评分）是测序的绝佳替代品。无论年龄，位置和H3K27M状态如何，预后仍然不佳。需要探索潜在的治疗目标。