Test Catalog

Test ID: HISME    
Histone H3 Trimethyl K27 Immunostain, Technical Component Only

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of malignant peripheral nerve sheath tumors and diffuse midline gliomas H3 K27M-mutant

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For the initial technical component only immunohistochemical (IHC) stain performed, the appropriate bill-only test ID will be reflexed and charged (IHTOI). For each additional technical component only IHC stain performed, an additional bill-only test ID will be reflexed and charged (IHTOA).

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Histone H3 trimethyl-K27 is a bivalent epigenetic regulator that silences or represses the gene. Evaluation of H3 trimethyl-K27 immunohistochemical expression is a helpful biomarker in the diagnosis of diffuse midline gliomas H3 K27M-mutant, which most frequently occur in children and with less frequency in adults. These tumors typically occur along the midline and include intrinsic pontine gliomas (DIPG), thalamic, and spinal cord diffuse gliomas. H3 K27M mutations lead to global reduction in H3 trimethyl-K27 and result in H3 trimethyl-K27 loss of expression.


Histologic mimics can be distinguishable from malignant peripheral nerve sheath tumors that show H3 trimethyl-K27 loss of expression.

Interpretation Provides information to assist in interpretation of the test results

This test does not include pathologist interpretation, only technical performance of the stain. If interpretation is required order PATHC / Pathology Consultation for a full diagnostic evaluation or second opinion of the case.


The positive and negative controls are verified as showing appropriate immunoreactivity and documentation is retained at Mayo Clinic Rochester. If a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is available upon request; call 855-516-8404.


Interpretation of this test should be performed in the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Age of a cut paraffin section can affect immunoreactivity. Stability thresholds vary widely among published literature and are antigen dependent. Best practice is for paraffin sections to be cut within 6 weeks.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Prieto-Granada CN, Wiesner T, Messina JL, et al: Loss of H3K27me3 Expression Is a Highly Sensitive Marker for Sporadic and Radiation-induced MPNST. Am J Surg Pathol. 2016;40(4):479-489

2. Schaefer IM, Fletcher C, Hormick JL: Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics. Mod Pathol. 2016;29:4-13

3. Lee W, Teckie S, Wiesner T, et al: PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Gene. 2014;46(11):1227-1232