Lorena Gurrieri1,2, Elisa De Carlo1,3, Lorenzo Gerratana1,4, Giovanna De Maglio5, Marianna Macerelli1, Federica Edith Pisa6,7, Elena Masiero5, Giuseppe Aprile1,8, Alessandro Follador1, Fabio Puglisi3,4, Gianpiero Fasola1, Simona Rizzato1, Stefano Pizzolitto5. 1. Department of Oncology, University Hospital of Udine, Udine 33100, Italy. 2. Department of Oncology, ASUITS University Hospital, Trieste 34129, Italy. 3. Department of Clinical Oncology, CRO Aviano National Cancer Institute, Aviano 33081 (PN), Italy. 4. Department of Medicine (DAME), The University of Udine, Udine 33100, Italy. 5. Department of Pathology, University Hospital of Udine, Udine 33100, Italy. 6. Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. 7. Department of Hospital Services, University Hospital of Udine, Udine, Italy. 8. Department of Oncology, San Bortolo General Hospital, ULSS8 Berica, East District, Vicenza 36100, Italy.
Abstract
AIM: MGMT promoter methylation has been associated with improved survival in glioblastoma multiforme treated with temozolomide. However, there is no consensus on specific cut-off levels of methylation. The aims of the study were to explore the prognostic impact of MGMT methylation status and to analyze the role of specific cut-off values. MATERIALS & METHODS: We analyzed 108 glioblastoma multiforme patients treated between 2008 and 2013 stratified according to three pyrosequencing-based quantitative methylation in: unmethylated (methylation <9%), intermediate (9-29%) and highly methylated (>29%). RESULTS: The three-class stratification has a prognostic impact (median progression-free survival: 7.97, 11.6 and 15 months respectively; p = 0.004; median OS: 13.2, 15.8 and 19.5 months, respectively; p = 0.0002), especially in patients exposed to temozolomide. CONCLUSION: Our study confirmed that the independent prognostic role of MGMT methylation status. An average level of methylation between all investigated CpGs of 9% may help discriminating between methylated and unmethylated tumors.
AIM: MGMT promoter methylation has been associated with improved survival in glioblastoma multiforme treated with temozolomide. However, there is no consensus on specific cut-off levels of methylation. The aims of the study were to explore the prognostic impact of MGMT methylation status and to analyze the role of specific cut-off values. MATERIALS & METHODS: We analyzed 108 glioblastoma multiformepatients treated between 2008 and 2013 stratified according to three pyrosequencing-based quantitative methylation in: unmethylated (methylation <9%), intermediate (9-29%) and highly methylated (>29%). RESULTS: The three-class stratification has a prognostic impact (median progression-free survival: 7.97, 11.6 and 15 months respectively; p = 0.004; median OS: 13.2, 15.8 and 19.5 months, respectively; p = 0.0002), especially in patients exposed to temozolomide. CONCLUSION: Our study confirmed that the independent prognostic role of MGMT methylation status. An average level of methylation between all investigated CpGs of 9% may help discriminating between methylated and unmethylated tumors.
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