MGMT testing for glioma in clinical laboratories: discordance with methylation analyses prevents the implementation of routine immunohistochemistry

Abstract

Purpose: Glioblastoma is a universally fatal cancer of the central nervous system which responds poorly to treatment. MGMT has potential as a predictive biomarker in glioblastoma patients to determine treatment response. However, methods of measuring MGMT are currently unsatisfactory, and as such, use of this marker has not translated well into the clinic. This paper aims to review current methodology of MGMT measurement, with a focus on immunohistochemistry as a potential way forward. TOPICS AND METHODS: Studies of glioma patients where MGMT immunohistochemistry was undertaken, as well as the literature surrounding methylation analyses and the regulation of MGMT, were reviewed.

Results: All methods of measuring MGMT were disputed in some way in the literature. A trend of discordance between methylation analyses and protein analyses was present. There is a lack of standardisation in the measurement of MGMT, and as a result, it seems that there are highly variable results.

Conclusions: No single method of MGMT analysis has emerged as a clear choice for routine clinical testing of MGMT in glioma patients. Although methylation analyses are favoured, their expense and inaccessibility are barriers to their use in routine clinical practice. More research into immunohistochemistry is needed to determine whether it can serve as a reliable and cost-effective alternative to methylation analyses.

Fig. 1

MGMT immunohistochemistry results discordant with methylation analyses