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Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis
Odense Univ Hosp, Denmark.
Odense Univ Hosp, Denmark.
Odense Univ Hosp, Denmark.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.ORCID iD: 0000-0001-8410-4939
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2018 (English)In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 44, no 2, p. 172-184Article in journal (Refereed) Published
Abstract [en]

Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status. Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population-based Region of Southern Denmark (RSD)cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM-patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules. Results: When divided at the median, patients with low expression of MGMT protein (AF-low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS-cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF-low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF-low had the best outcome; median OS 23.1 and 20.0 months, respectively. Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour-specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

Place, publisher, year, edition, pages
WILEY , 2018. Vol. 44, no 2, p. 172-184
Keywords [en]
glioblastoma multiforme; glioma; image analysis; MGMT; O-6-methylguanine-DNA methyltransferase; prognosis
National Category
Clinical Laboratory Medicine
Identifiers
URN: urn:nbn:se:liu:diva-145797DOI: 10.1111/nan.12415ISI: 000425641000006PubMedID: 28574607OAI: oai:DiVA.org:liu-145797DiVA, id: diva2:1192392
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-05-02

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Malmström, AnnikaLysiak, MalgorzataSöderkvist, PeterRosell, Johan
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Division of Cell BiologyFaculty of Medicine and Health SciencesDepartment of Advanced Home Care in LinköpingDepartment of Clinical Pathology and Clinical GeneticsDivision of Clinical SciencesRegional Cancer Center South East Sweden
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Neuropathology and Applied Neurobiology
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