Use of immunohistochemical surrogate biomarkers as an alternativeto molecular methods in classifying adult-type diffuse gliomas

Adult-type IDH (isocitrate dehydrogenase)-mutant diffuse gliomas are divided into two groups as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q codeleted, on the basis of 1p/19q status. According to the 2021 World Health Organization (WHO) classification; astrocytomas containing CDKN2A/B homozygous deletion (HD) are graded as grade 4 even in the absence of microvascular proliferation and/or necrosis. Nowadays, the use of difficult-to-access and expensive molecular methods has become mandatory in the diagnosis and grading of IDH-mutant diffuse gliomas. In this study, we aimed to find accessible and cheap immunohistochemical (IHC) surrogate biomarkers that could be an alternative to molecular methods. Tissue microarrays were prepared using 93 astrocytoma and 73 oligodendroglioma cases diagnosed between 2014-2021 in Hacettepe University Department of Medical Pathology. 1p/19q and CDKN2A FISH and H3K27me3 and MTAP IHC studies were performed and two observers evaluated the staining. The relationship between CDKN2A HD and loss of MTAP expression and the relationship between 1p/19q codeletion and loss of H3K27me3 expression were investigated. CDKN2A HD was detected in 25 (15.1%) of 161 diffuse gliomas, while the first observer detected MTAP loss in 30 (18.1%) out of 164, and the second observer in 29 (17.5%). As an alternative to CDKN2A FISH, the sensitivity and specificity of MTAP were calculated as 88% and 95.52-96.27%. Loss of H3K27me3 expression was observed in 67.1-68.5% of oligodendrogliomas, and 21.1-22.6% of astrocytomas. As an alternative to 1p/19q FISH, the sensitivity of H3K27me3 was 77.42-76.34% and the specificity as 65.75%-67.12%. In conclusion, MTAP IHC appears to be a reliable surrogate biomarker to CDKN2A FISH however loss of H3K27me3 expression is not sensitive and specific enough as an alternative to 1p/19q FISH.