TY - JOUR
T1 - Immunohistochemistry for O6-methylguanin-DNA methyltransferase in glioblastomas defined by WHO2016
T2 - Correlation with promoter methylation status and patients’ progression-free survival with the cut-off value determined by ROC analysis
AU - Pareira, Eriel Sandika
AU - Kitano, Yuki
AU - Ohara, Kentaro
AU - Kanazawa, Tokunori
AU - Nakagawa, Yu
AU - Yoshida, Kazunari
AU - Sasaki, Hikaru
PY - 2020/3
Y1 - 2020/3
N2 - Although promoter methylation status is known to correlate with response to alkylating agents, immunohistochemistry (IHC) is the only available method for MGMT status in many institutions. However, the clinical utility of MGMT IHC is controversial. A hundred and twenty four cases of primary glioblastoma diagnosed by morphology-based criteria over 2 decades were re-appraised based on WHO 2016 classification. Tumor MGMT status was evaluated by IHC and methylation-specific PCR (MSP) to see if any correlation between the results of the 2 methods. The association with patients’ prognoses was also investigated. Among 124 cases, 116 were confirmed to be glioblastoma by definition of WHO2016, and median overall survival (OS) of glioblastoma, IDH-wildtype and epithelioid glioblastoma were 18 and 27 months, respectively. MGMT promoter methylation status significantly correlated with progression-free survival (PFS) (p = 0.014) but not with OS (p = 0.364) in patients with glioblastoma by the integrated diagnosis. With the cut-off value of 24.5% of positive cell ratio as determined by receiver operating characteristic (ROC) analysis, there was a good correlation between the results of IHC and MSP (p = 0.08 × 10−24). Accordingly, there was a marginal association between the results of IHC and patients’ PFS (p = 0.063), but not OS (p = 0.563). When the patients were divided into pre and post temozolomide era, the association of MGMT promoter methylation status with PFS was only noted in the patients of temozolomide era (pre, p = 0.432; post, p = 0.015).
AB - Although promoter methylation status is known to correlate with response to alkylating agents, immunohistochemistry (IHC) is the only available method for MGMT status in many institutions. However, the clinical utility of MGMT IHC is controversial. A hundred and twenty four cases of primary glioblastoma diagnosed by morphology-based criteria over 2 decades were re-appraised based on WHO 2016 classification. Tumor MGMT status was evaluated by IHC and methylation-specific PCR (MSP) to see if any correlation between the results of the 2 methods. The association with patients’ prognoses was also investigated. Among 124 cases, 116 were confirmed to be glioblastoma by definition of WHO2016, and median overall survival (OS) of glioblastoma, IDH-wildtype and epithelioid glioblastoma were 18 and 27 months, respectively. MGMT promoter methylation status significantly correlated with progression-free survival (PFS) (p = 0.014) but not with OS (p = 0.364) in patients with glioblastoma by the integrated diagnosis. With the cut-off value of 24.5% of positive cell ratio as determined by receiver operating characteristic (ROC) analysis, there was a good correlation between the results of IHC and MSP (p = 0.08 × 10−24). Accordingly, there was a marginal association between the results of IHC and patients’ PFS (p = 0.063), but not OS (p = 0.563). When the patients were divided into pre and post temozolomide era, the association of MGMT promoter methylation status with PFS was only noted in the patients of temozolomide era (pre, p = 0.432; post, p = 0.015).
KW - Glioblastoma
KW - Immunohistochemistry
KW - MGMT
KW - Methylation
KW - PFS
UR - http://www.scopus.com/inward/record.url?scp=85079551773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079551773&partnerID=8YFLogxK
U2 - 10.1016/j.jocn.2020.01.088
DO - 10.1016/j.jocn.2020.01.088
M3 - Article
C2 - 32070670
AN - SCOPUS:85079551773
VL - 73
SP - 231
EP - 236
JO - Journal of Clinical Neuroscience
JF - Journal of Clinical Neuroscience
SN - 0967-5868
ER -