MGMT promoter methylation status in glioblastoma (GBM) patients: a quantitative pyrosequencing approach and its prognostic role

Date

09 Oct 2016

Session

Poster display

Presenters

Ardi Pambuku

Citation

Annals of Oncology (2016) 27 (6): 103-113. 10.1093/annonc/mdw367

Authors

A. Pambuku1, G. Lombardi1, R. Bertorelle2, L. Bellu1, P. Fiduccia2, M. Gardiman3, A. Della Puppa4, F. Berti5, D. D'Avella6, V. Zagonel1

Author affiliations

  • 1 Department Of Clinical And Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology, 35100 - Padova/IT
  • 2 Department Of Clinical And Experimental Oncology, Clinical Trials And Biostatistics Unit And Molecular Immunology And Oncology Unit, Istituto Oncologico Veneto IRCCS, Padova/IT
  • 3 Deaprtment Of Pathology, Azienda Ospedaliera Padova, 35100 - Padova/IT
  • 4 Neurosurgery Department, Azienda Ospedaliera Padova, 35100 - Padova/IT
  • 5 Radiotherapy, Veneto Institute of Oncology, 35100 - Padova/IT
  • 6 Neurosurgery Department, University of Padova, 35100 - Padova/IT
More

Resources

Background

MGMT gene promoter methylation status is acknowledged as a prognostic factor and predictive marker for temozolomide (TMZ) treatment. Although MGMT status determined by pyrosequencing was showed to correlate with progression free survival (PFS) and overall survival (OS), it is still unclear a cut-off value that discriminates between methylated and unmethylated patient (pts) and its correlation with the patient clinical outcome.

Methods

We analyzed the tissue samples from 128 PTS diagnosed with GBM from November 2009 to December 2015. All PTS underwent treatment with RT + TMZ and had an ECOG-PS 0-2. Methylation percentage for each sample was obtained by calculating the average methylation of all 10CpG sites (75-84) of MGMT promoter by pyrosequencing analysis. PTS with 0-6% of methylation were classified as unmethylated (UM), PTS with 7-24% as low methylated (LM) and PTS with ≥ 25% as high methylated (HM). 25% was the median value of methylation of our PTS having >6% of methylation.

Results

Median age was 60 yrs (range 25-84), 60.9% were male, 74.2% had an ECOG PS 0-1, 50.8% underwent radical surgery, 85 PTS were dead at the time of analysis. 75 PTS (58.6%) were UM, 26 PTS (20,3%) were LM and 27 PTS (21,1%) were HM. On univariate analysis HM, LM and UM showed a PFS of 15.8, 10 and 9.1 ms, respectively (p = 0.1). OS was 38.7, 21 and 18.8ms (p= 0.06). On multivariate analysis UM and LM PTS had a statistically lower PFS vs HM PTS (HR = 2.57; p = 0.001; HR= 2.5; p = 0.007, respectively) and statistically lower OS (HR = 3.47; p 

Conclusions

MGMT promoter methylation status determined by pyrosequencing analysis may correlate to PFS and OS. We found a cut-off of 25% of methylation which determined two sub-groups of PTS having different clinical outcome; in particular, HM PTS had a significant longer PFS and OS.

Clinical trial identification

Legal entity responsible for the study

IOV

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings