TO MGMT TEST OR NOT?

A posting by one of the advisors to the IBTA to a US-based email discussion group. (December 2008)

"Just a word of caution re "MGMT testing".

There are different types of MGMT testing. Many pathology labs can do immunohistochemistry (IHC) testing for MGMT expression but you need to be aware that this is not the same test done in the EORTC/NCIC phase III trial (Stupp trial) for TMZ+RT. The MGMT test performed in conjunction with this trial (Hegi et al.) is methylation specific PCR (MSP) which tests whether the promoter region of the MGMT gene is methylated (switched off) or unmethylated (switched on). The two tests do not correlate exactly and there is disagreement among the professionals (both clinicians and researchers) as to which test to use.

My understanding is that MSP is currently considered the best test and this will be the test used in the forthcoming phase III CENTRIC trial for cilengitide in newly diagnosed GBM. However MSP is not routinely used in the clinic and is mainly restricted to the research setting such as clinical trials. There is a third method - the Kolling Institute in Sydney have tested MGMT methylation status using gene sequencing but again they are involved only in research and do not run a clinic.

More importantly, what will you do with the test results? How will it change your treatment plan? Even patients with a methylated MGMT promoter (MGMT positive in IHC test) may benefit from TMZ. I am not aware of any alternative, preferred treatment plans for unmethylated patients. The worst case scenario is a test result of unmethylated MGMT and your doctors refusing to prescribe TMZ, or insurance refusing to pay, based on this result.

I don't want to put anybody off getting MGMT testing but I think people need to be aware of the above issues before proceeding."

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