title: Immunohistochemical evaluation of O6 -methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma.
abstract: Temozolomide (TMZ) is an oral alkylating agent which is widely used in the treatment of glioblastoma (GBM) and is composed of astrocytic and/or oligodendroglial tumors, and the evaluation of O(6) -methylguanine DNA methyltransferase (MGMT) expression is important to predict the response to TMZ therapy. In this study, we conducted immunohistochemical analysis of 117 cases of Japanese GBM including 19 cases of GBM with oligodendroglioma component (GBMO), using a scoring system for quantitative evaluation of staining intensity and proportion of MGMT, and performed survival analysis of these patients. Immunohistochemically, 55 cases (47%) were positive for MGMT with various intensities and proportions (total score (TS) ≥ 2), while 62 cases (53%) were negative (TS = 0). The distribution of MGMT expression pattern was not affected by any clinicopathological parameters such as the histological subtype (GBM vs. GBMO), age and gender. The survival analysis of these patients revealed that the minimal expression of MGMT (TS ≥ 2) was a significant unfavorable prognostic factor (P < 0.001) as well as resectability (P = 0.004). Moreover, multivariate analysis showed that minimal MGMT expression in GBM was the most potent independent predictor for progression free survival (P < 0.001) and also overall patient survival (P < 0.001). This is the first report employing the scoring system for both staining intensity and proportion to evaluate immunohistochemical MGMT expression in GBM. In addition, our results emphases the clinicopathological values of the immunohistochemical approach for MGMT expression in glioma patients as a routine laboratory examination.
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Terasaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Tamio
authors.initials: T
authors.lastname: Ito
authors.forename: Yuuta
authors.initials: Y
authors.lastname: Kamoshima
authors.forename: Shin
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Sadao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Masahito
authors.initials: M
authors.lastname: Katoh
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ishii
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mohri
authors.forename: Mishie
authors.initials: M
authors.lastname: Tanino
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000032:analysis* / Q000096:biosynthesis*; D015996:Survival Rate / Q000639:trends
chemical_list: D014408:Biomarkers, Tumor; D019853:O(6)-Methylguanine-DNA Methyltransferase
keywords: MGMT; glioblastoma; immunohistochemistry; survival analysis; temozolomide