Diffuse glial tumors harbor important molecular alterations which have roles for the classification, prognostication, and prediction of therapeutic response. These molecular alterations are ideally checked by DNA sequencing methods. However, it is not always possible to create a molecular pathology laboratory with enough equipment, competent staff, and validated methods or it is not always possible to perform the expensive diagnostic molecular tests. At this point, most of the pathologists all over the world prefer or have to use immunohistochemical technics to detect molecular alterations. There are many immunohistochemical stains which are useful surrogate markers for specific molecular alterations in central nervous system tumors. As the types of molecular alterations are in a broad spectrum (point mutation, deletion, amplification, translocation, hypermethylation); the meaning of the presence/absence or subcellular localization of a protein product should be explained with the knowledge of the expected molecular alteration and the associated protein expression pattern. Every finding, during diagnostic work-up of a diffuse glioma, is a piece of the puzzle. Therefore the immunohistochemical result of a particular stain must be interpreted in context with clinical, radiologic, morphologic, and other immunohistochemical findings.
