Combining MGMT promoter pyrosequencing and protein expression to optimize prognosis stratification in glioblastoma

Abstract

Pyrosequencing (PSQ) represents the golden standard for MGMT promoter status determination. Binary interpretation of results based on the threshold from the average of several CpGs tested would neglect the existence of the “gray zone”. How to define the gray zone and reclassify patients in this subgroup remains to be elucidated. A consecutive cohort of 312 primary glioblastoma patients were enrolled. CpGs 74‐81 in the promoter region of MGMT were tested by PSQ and the protein expression was assessed by immunohistochemistry (IHC). Receiver operating characteristic curves were constructed to calculate the area under the curves (AUC). Kaplan‐Meier plots were used to estimate the survival rate of patients compared by the log‐rank test. The optimal threshold of each individual CpG differed from 5% to 11%. Patients could be separated into the hypomethylated subgroup (all CpGs tested below the corresponding optimal thresholds, n = 126, 40.4%), hypermethylated subgroup (all CpGs tested above the corresponding optimal thresholds, n = 108, 34.6%), and the gray zone subgroup (remaining patients, n = 78, 25.0%). Patients in the gray zone harbored an intermediate prognosis. The IHC score instead of the average methylation levels could successfully predict the prognosis for the gray zone (AUC for overall survival, 0.653 and 0.519, respectively). Combining PSQ and IHC significantly improved the efficiency of survival prediction (AUC: 0.662, 0.648, and 0.720 for PSQ, IHC, and combined, respectively). Immunohistochemistry is a robust method to predict prognosis for patients in the gray zone defined by PSQ. Combining PSQ and IHC could significantly improve the predictive ability for clinical outcomes.

Temozolomide and Capecitabine Treatment for an Aggressive Somatotroph Pituitary Tumor: A Case Report and Literature Review

“…There have been 11 cases, including our two, describing both TMZ treatment outcomes and the degree of MGMT expression, in aggressive or malignant somatotroph tumors; the summary of these cases is shown in Table 1 ( 9 , 10 , 19 – 22 ). Several previous studies showed the correlation between MGMT promoter methylation and protein expressions in IHC ( 23 , 24 ), and it is thought that unmethylated MGMT promotor most leads to strong expressions in IHC ( 23 , 24 ). Two cases which analyzed the promoter methylation status reported unmethylated MGMT promoters ( 20 , 22 ); and nine cases reported strong expression of MGMT.…”

From Patient to Musician: A Multi-Sensory Virtual Reality Rehabilitation Tool for Spatial Neglect

“…USN is relatively common and has many causes, including neurodegenerative diseases, neoplasm, aneurysm, traumatic brain injury after the surgical resection of a brain tumour and stroke, where stroke is by far the most prevalent cause [4,[12][13][14]. Left-sided neglect is more common than right-sided neglect, as it is mostly linked to damage to the right hemisphere of the brain [15,16].…”

T2/FLAIR Abnormity Could be the Sign of Glioblastoma Dissemination

“…The 1p/19q codeletion, 7+/10-, epidermal growth factor receptor (EGFR) amplification status were determined by fluorescence in situ hybridization (FISH). For IDH1 R132 and IDH2 R172 mutations, telomerase reverse transcriptase (TERT) promoter C228T/C250T mutation was tested by Sanger sequencing (18,19). The status of O 6 -methylguanine-DNA methyltransferase (MGMT) promoter was determined by pyrosequencing, and patients were divided into methylated and unmethylated by the average methylation level of 12% (20).…”

“…We also employed the principles of RANO for low-grade glioma to evaluate the dynamic change of T2/FLAIR of this GBM cohort (21). MR spectrum (MRS), perfusion-weighted MRI (PWI) by dynamic susceptibility contrast (DSC), and 18 F-FDG-PET MRI were available to some but not all patients during the follow-up to provide valuable information to distinguish treatment response (pseudoprogression and radiation necrosis) from true progression.…”