The PFA molecular subgroup of posterior fossa ependymomas (PF-EPNs) shows poor outcome. H3K27me3 (me3) loss by immunohistochemistry (IHC) is a surrogate marker for PFA wherein its loss is attributed to overexpression of Cxorf67/EZH2 inhibitory protein (EZHIP), C17orf96, and ATRX loss. We aimed to subgroup PF-EPNs using me3 IHC and study correlations of the molecular subgroups with other histone related proteins, 1q gain, Tenascin C and outcome. IHC for me3, acetyl-H3K27, H3K27M, ATRX, EZH2, EZHIP, C17orf96, Tenascin-C, and fluorescence in-situ hybridisation for chromosome 1q25 locus were performed on an ambispective PF-EPN cohort (2003–2019). H3K27M-mutant gliomas were included for comparison. Among 69 patients, PFA (me3 loss) constituted 64%. EZHIP overexpression and 1q gain were exclusive to PFA seen in 72% and 19%, respectively. Tenascin C was more frequently positive in PFA (p = 0.02). H3K27M expression and ATRX loss were noted in one case of PFA–EPN each. All H3K27M-mutant gliomas (n = 8) and PFA-EPN (n = 1) were EZHIP negative. C17orf96 and acetyl-H3K27 expression did not correlate with me3 loss. H3K27me3 is a robust surrogate for PF-EPN molecular subgrouping. EZHIP overexpression was exclusive to PFA EPNs and was characteristically absent in midline gliomas and the rare PFA harbouring H3K27M mutations representing mutually exclusive pathways leading to me3 loss.

颅后窝室间隔瘤（PF-EPNs）的PFA分子亚组显示不良预后。H3K27me3（me3）免疫组织化学（IHC）丢失是PFA的替代标志物，其丢失归因于Cxorf67 / EZH2抑制蛋白（EZHIP），C17orf96和ATRX丢失的过度表达。我们旨在使用me3 IHC将PF-EPNs进行亚组化，并研究该分子亚组与其他组蛋白相关蛋白，1q增益，腱生蛋白C和结局的相关性。在不确定的PF-EPN队列中（2003-2019年）对me3的IHC，乙酰基H3K27，H3K27M，ATRX，EZH2，EZHIP，C17orf96，腱生蛋白C和染色体1q25基因座的荧光原位杂交进行了研究。包括H3K27M突变型神经胶质瘤进行比较。在69例患者中，PFA（me3丢失）占64％。EZHIP过表达和1q增益是PFA独有的，分别占72％和19％。p  = 0.02）。分别在1例PFA-EPN中记录了H3K27M表达和ATRX丢失。所有H3K27M突变型神经胶质瘤（n  = 8）和PFA-EPN（n  = 1）均为EZHIP阴性。C17orf96和乙酰基H3K27表达与me3丢失无关。H3K27me3是PF-EPN分子亚组的可靠替代品。EZHIP过度表达是PFA EPN所独有的，在中线神经胶质瘤和罕见的具有H3K27M突变的PFA中不存在，这代表导致me3丢失的互斥途径。