The Prognostic Value of Pyrosequencing-Detected MGMT Promoter Hypermethylation in Newly Diagnosed Patients with Glioblastoma.
O6-methylguanine-DNA-methyltransferase (MGMT) has emerged as a relevant predictor of therapeutic response and good prognosis in patients with glioblastoma (GBM). Transcriptionally active MGMT rapidly removes the alkyl adducts, preventing the formation of cross-links and thereby causing resistance to alkylating drugs. Studies with pyrosequencing (PSQ) showed that this technique has a higher reproducibility and sensitivity than other techniques. However, the definition of a prognostically relevant threshold for the percentage of MGMT methylation remains one of the most critical issues in the use of PSQ analysis. The aim of this study was to define the cut-off value correlated with good favourable prognostic outcomes. We retrospectively analyzed 51 patients (33 males, 18 females) with GBM who underwent surgery or biopsy. The Receiver Operating Characteristics analysis showed that the best possible criteria for PSQ-detected percentage of MGMT methylation that predicted progression-free survival (PFS) and overall survival (OS) were 19% and 13%, respectively. Patients with ≤ 19% of PSQ-detected MGMT had a shorter PFS (HR: 0.24, p < 0.01); those ones with ≤ 13% had a shorter OS (HR: 0.33, p < 0.05). Our study reinforces the importance of MGMT in the management of GBM patients, but future studies with larger sample sizes are warranted to confirm our findings.
Neuro-Oncology Unit, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Veronica
V
Villani
Division of Pathology, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Beatrice
B
Casini
Neuro-Oncology Unit, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Andrea
A
Pace
Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università 30, 00185 Rome, Italy.
Luca
L
Prosperini
Division of Neurosurgery, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Carmine M
CM
Carapella
Service of Neuroradiology, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Antonello
A
Vidiri
Division of Medical Oncology, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Alessandra
A
Fabi
Division of Pathology, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Mariantonia
M
Carosi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes