Clinical neuropathology practice guide 1-2013: Molecular subtyping of glioblastoma: ready for clinical use?

Recently, integrated genome-wide analyses have revealed several glioblastoma (GB) subtypes, which differ in terms of key pathogenetic pathways and point to different cells of origin. Even though the proneural and mesenchymal GB signatures evolved as most robust, there is no consensus on the exact number of subtypes and defining criteria. Moreover, important issues concerning within-tumor heterogeneity and class-switching upon recurrence remain to be addressed. Early evidence indicates an association of different GB subtypes with patient outcome and response to therapy, which argues for the implementation of molecular GB subtyping, and consideration of GB subtypes in subsequent patient management. As genome-wide analyses are not routinely available to the majority of neuropathology laboratories, first attempts to implement immunohistochemical testing of surrogate markers are underway. However, so far, confirmatory studies are lacking and there is no consensus on which markers to use. Further, the rationale for testing is compromised from a clinical point of view by a lack of effective therapies for individual GB subtypes. Thus, incorporation of genomic research findings as a basis for GB patient management and clinical decision making currently remains a perspective for the future.