Advances in the management of gliomas: molecular predictors of outcome
Prof. Dr. Michael Weller
28 slide(s) – 00:21:19– English –2010-09-27
Gliomas, which are differentiated by morphological criteria defined in theWHO classification, are also characterized by distinct molecular alterations. Mutations of p53 and the isocitrate dehydrogenase (IDH) 1/2 genes are more common in gliomas ofWHO grades I-III whereas amplification of the epidermal growth factor receptor (EGFR) and phosphataseand-tensin homolog (PTEN) genes are more common in glioblastoma. The high rate of IDH mutations in grade II/III gliomas of 80% and the rate of below 15% in glioblastoma prove that most glioblastomas do not evolve via malignant progression of lower grade gliomas. Resection and postoperative radiotherapy have been the cornerstones of treatment for gliomas. Temozolomide has been defined as a novel standard of care when combined with radiotherapy in newly diagnosed glioblastoma. In contrast, temozolomide alone has become an alternative to radiotherapy alone in patients with grade II and III gliomas. Methylation of the promoter region of the O6-methylguanylmethyltransferase (MGMT) gene has emerged as a potent specific predictor of benefit from temozolomide chemotherapy in glioblastoma patients, but not patients with grade III gliomas who appear to benefit equally from chemotherapy or radiotherapy if their tumour exhibits MGMT promoter methylation. Similarly, 1p/19q deletions and IDH-1 mutations are favourable predictors of outcome in patients receiving adjuvant therapy, but not patients treated by surgery alone. Altogether, there has thus been made significant progress in molecular neuropathology, and the determination of a set of molecular markers will soon be implemented in the diagnosis and clinical decision making for patients with gliomas.