Zeta H3K27me3 Antibody. Zeta’s rabbit recombinant antibody recognizes H3K27me3, a nuclear epigenetic mark with important diagnostic value in surgical pathology, particularly in nerve sheath tumors, meningiomas, and certain pediatric tumors. H3K27me3 refers the trimethylation of lysine 27 on histone H3, a key epigenetic modification associated with gene regulation. Histone H3 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. The N-terminal tail of histone H3 can undergo several different types of epigenetic modifications that influence cellular processes. These modifications include the covalent attachment of methyl or acetyl groups to lysine and arginine amino acids and the phosphorylation of serine or threonine. Loss-of-function somatic alterations in different components of the polycomb repressive complex 2 (PRC2) occur in most malignant peripheral nerve sheath tumors (MPNSTs). These highly recurrent and specific inactivation of PRC2 components co-occurred with somatic alterations of CDKN2A and NF1. MPNSTs with PRC2 inactivation through EED or SUZ12 alterations showed consistent complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3) by IHC analysis. Approximately 90% of sporadic and radiation associated MPNSTs and 50% NF1-associated MPNSTs show loss of H3K27me3 expression. In addition, diffuse intrinsic pontine glioma and midline glioma also loss H3K27me3 expression.
In summary, H3K27me3 is a post-translational modification of histone H3 and is mediated by the Polycomb Repressive Complex 2 (PRC2), where EZH2 is the methyltransferase and where modification is associated with gene silencing and chromatin compaction.
In Malignant Peripheral Nerve Sheath Tumor (MPNST), loss of H3K27me3 nuclear staining is a frequent finding in high-grade MPNST, seen in both sporadic and NF1-associated MPNST and is helpful in distinguishing MPNST from histologic mimics such as cellular schwannoma or fibrosarcoma. Conversely, in Meningiomas, H3K27me3 is retained and loss of H3K27me3 expression in meningiomas has been correlated with increased risk of recurrence, particularly in WHO grade 2–3 tumors.
In pedistric brain and soft tissue tumors, some diffuse midline gliomas have related histone mutations (H3K27M), which abolish H3K27me3 staining entirely and is useful for confirmation. Certain sarcomas or embryonal tumors may show alterations affecting PRC2 function and H3K27me3 levels but it is seen in both sporadic and NF1-associated MPNST and can be helpful in distinguishing MPNST from histologic mimics such as cellular schwannoma or fibrosarcoma.
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