Molecular diagnostic testing in malignant gliomas: a practical update on predictive markers

Advances in understanding the molecular underpinnings of cancer and in molecular diagnostic technologies have changed the clinical practice of oncologic pathology. The development of targeted therapies against specific molecular alterations in cancer further portends changes in the role of the pathology laboratory to guide such custom therapies. To reconcile the flood of scientific discoveries in this area, the promises of highly touted novel therapeutics, and the practicality of applying this knowledge to the day-to-day practice of clinical neuropathology, the present review highlights the operative differences between diagnostic, predictive, and prognostic markers, and discusses issues surrounding the transition of prospective biomarkers to routine laboratory implementation. This review focuses on 3 predictive molecular markers that are either in clinical use or are contemplated for use in the evaluation of malignant gliomas: assessment of 1p/19q loss in oligodendroglial tumors, examination of O6-methylguanine DNA methyltransferase promoter methylation status in glioblastomas, and molecular dissection of the epidermal growth factor receptor-phosphatidylinositol 3-kinase pathway in glioblastomas. Implementation of such predictive markers is not straightforward and requires critical review of the available literature and attention to practical laboratory, compliance, financial, and clinical management issues.