Abstract
O6-Methylguanine-DNA methyltransferase (MGMT) represents a major mechanism of resistance of diffuse gliomas against alkylating agents. In glioblastoma, the most frequent and most malignant diffuse astrocytoma, hypermethylation of the MGMT promoter is found in 40–50% of cases and has been linked to improved survival after alkylating chemotherapy. MGMT promoter hypermethylation is expected to result in an inhibition of MGMT protein synthesis. The immunohistochemical investigation of MGMT protein in surgical specimens has been suggested to represent an easy approach to assess response to alkylating agents and several initial studies found strong associations of MGMT immunohistochemistry and patient outcome. Subsequent studies with concordant metholodical approaches could not confirm these associations. As possible reasons for these discordant results, technical aspects of MGMT immunohistochemistry, as well as admixed MGMT positive reactive astrocytes, lymphocytes and macrophages/microglia have been proposed. Despite some indication of an association of MGMT immunohistochemistry and survival, the method can currently not be recommended for evaluation of patient outcome or possible response to alkylating agents in diffuse astrocytomas.
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Capper, D. (2012). Diffuse Astrocytomas: Immunohistochemistry of MGMT Expression. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 5. Tumors of the Central Nervous System, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2019-0_10
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