Immunohistochemical comparative analysis of GFAP, MAP - 2, NOGO - A, OLIG - 2 and WT - 1 expression in WHO 2016 classified neuroepithelial tumours and their prognostic value

Immunohistochemistry is routinely used in differential diagnosis of tumours of the central nervous system (CNS). The latest 2016 WHO 2016 revision now includes molecular data such as IDH mutation and 1p/19q codeletion thus restructuring glioma classification. Direct comparative information between commonly used immunohistochemical markers for glial tumours GFAP, MAP - 2, NOGO - A, OLIG - 2 and WT - 1 concerning quality and quantity of expression and their relation to the new molecular markers are lacking. We therefore compared the immunohistochemical staining results of all five antibodies in 34 oligodendrogliomas, 106 ependymomas and 423 astrocytic tumours. GFAP expression was reduced in cases with higher WHO grade, oligodendroglial differentiation and in IDH wildtype diffuse astrocytomas. By contrast MAP - 2 expression was significantly increased in diffuse astrocytomas with IDH mutation, while NOGO - A expression was not associated with any molecular marker. WT - 1 expression was significantly decreased in tumours with IDH mutation and ATRX loss. OLIG - 2 was increased in IDH-mutant grade II astrocytomas and in cases with higher proliferation rate. In univariate survival analysis high WT - 1 expression was significantly associated with worse outcome in diffuse astrocytic tumours (log rank p < 0.0001; n = 211; median time: 280 days vs 562 days). None of the markers was prognostic in multivariate survival analysis. Among the evaluated markers MAP - 2, OLIG - 2 and WT - 1 showed the best potential to separate between glioma entities and can be recommended for a standardized immunohistochemical panel.