The molecular pathology of primary brain tumors

As the molecular basis of brain neoplasia continues to be elucidated, the pathologist is called upon more and more to provide not only a morphological diagnosis according to classic concepts, but also molecular data that offer additional information in terms of biological behavior and potential treatment response. In this review, we discuss the major brain tumor subtypes, some diagnostic issues that emphasize the need for molecular data, and existing putative molecular pathways associated with brain tumor subtypes. We further discuss the role of molecular tumor signatures as a means of determining prognosis and response to specific therapies. At present, it appears that 1p/19q assessment, as well as immunohistochemistry for IDH1 and β-catenin, should be available to all anatomic pathology laboratories that accession brain tumors. O-methyl-guanine-DNA methyltransferase methylation analysis is an additional consideration for glioblastoma, although clinicians and patients may choose to forego this analysis if temozolomide will be used regardless of methylation status. Given the evolving nature of cancer biology and progress toward personalized medicine, it is likely, if not axiomatic, that molecular tumor characterization with continues to expand on a routine basis.