Wednesday, February 17, 2016

Immunohistochemical surrogate for IDH1 mutation

Quoted highlights on IDH mutation IHC 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:

- IDH1 and IDH2 mutations are mutually exclusive events and indicate one of the early processes in gliomagenesis, before TP53 and ATRX mutations in astrocytic tumors, and before 1p/19q codeletion, CIC, and FUBP1 mutations in oligodendroglial tumors

- IDH mutations exist in at least 70% of diffuse gliomas, particularly World Health Organization (WHO) grade II and III astrocytomas, oligodendrogliomas, and secondary glioblastomas, and are rarely present in other types of brain tumors

- Clinically, patients with either IDH1 orIDH2 mutations are younger and have a better prognosis in terms of both overall survival and progression-free survival compared to patients carrying wild-type IDH

Intriguingly, recent studies reveal similar age of onset and little differences in clinical outcome among IDH-mutant tumors previously classified as grade II and grade III astrocytomas by WHO 2007 criteria

- The “good effect” of having IDH mutation also applies to glioblastomas since patients with IDH-mutant glioblastomas have better clinical outcomes compared to those with grade III astrocytomas having wild-type IDH...

The presence of IDH mutations may argue in favor of a diagnosis of anaplastic glioma over primary glioblastoma given that the latter typically does not harbor the mutation

- The most useful antibodies detect the common mIDH1 R132H mutation, which is present in 90% of IDH-mutant gliomas

- Immunohistochemistry for mIDH1 R132H clone H09 shows 88%–100% concordance rate with IDH1 R132H mutational status determined by DNA sequencing


Agent 86 said...

Thanks, Brian.

I'm not great with math, but 90% concordance with the IDH1 base substitution recognized by the commercially available antibody (which occurs 90% of the time) suggests that IDH1-R132H IHC may miss about 1 in 5 IDH-mutated gliomas. I'd like to know what your molecularly adept/white-collar neuropathologist readers are doing with IDH1-R132H IHC negative tumors (especially non-GBMs).

It was also interesting to read that the commercial antibody may pick up a certain number of other IDH1 point mutations.


Brian E. Moore, MD, MEd said...

Not being a white-collar neuropathologist, I wouldn't know for sure. But, I would think that they might handle IDH1 IHC negative tumors by assuming they are indeed not mutated EXCEPT in cases where ATRX IHC nuclear staining is lost, in which case they would reflex to a molecular test to find either the IDH1 mutation missed by IDH1 IHC or non-canonical IDH mutations.

Thanks for commenting, Agent 86!