Quoted highlights on IHC mutational surrogates from: Tanboon J, Williams EA, and Louis DN. The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas. J Neuropathol Exp Neurol Vol. 75, No. 1, January 2016, pp. 4–18:
- K27M mutations in H3F3A [the gene encoding H3.3] and HIST1H3B [the gene encoding H3.1] occur in approximately 40%–80% of pediatric diffuse intrinsic pontine gliomas (DIPG) and 20% of nonbrainstem glioblastomas.
- The central role of these mutations in such tumors will result in these neoplasms being designated as “diffuse midline glioma, H3 K27M-mutant” in the 2016 WHO Classification of Tumours of the Central Nervous System
- The presence of K27M mutations in pediatric glioblastomas (including DIPG) is associated with shorter survival compared to the wild-type tumors... [T]he presence of K27M mutations can be used as a diagnostic marker and poor prognostic marker for pediatric high-grade astrocytoma.
- K27M mutations in both the H3.3 and H3.1 histones can be detected by immunohistochemistry using an anti-H3K27M antibody. Positivity can therefore be useful to establish a diagnosis of infiltrating glioma in lower-cellularity biopsies, and can be used to subtype and genotype these diffuse gliomas.
- The pattern of positivity is nuclear, with positivity in most of the tumor cells; nontumor cell nuclei are negative.
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