Immunohistochemical evaluation of O6-methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma

• Published in: Neuropathology Vol. 34; no. 3; pp. 268 - 276
• Main Authors: Miyazaki, Masaya, Nishihara, Hiroshi, Terasaka, Shunsuke, Kobayashi, Hiroyuki, Yamaguchi, Shigeru, Ito, Tamio, Kamoshima, Yuuta, Fujimoto, Shin, Kaneko, Sadao, Katoh, Masahito, Ishii, Nobuaki, Mohri, Hiromi, Tanino, Mishie, Kimura, Taichi, Tanaka, Shinya
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.06.2014; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - biosynthesis; Brain Neoplasms - enzymology; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Deoxyribonucleic acid; DNA; Female; Gene Expression Regulation, Neoplastic; glioblastoma; Glioblastoma - enzymology; Glioblastoma - mortality; Glioblastoma - pathology; Humans; immunohistochemistry; Male; MGMT; Middle Aged; Multivariate analysis; O-Methylguanine-DNA Methyltransferase - analysis; O-Methylguanine-DNA Methyltransferase - biosynthesis; Survival analysis; Survival Rate - trends; temozolomide; temozolomide; glioblastoma; immunohistochemistry; survival analysis; MGMT
• ISSN: 0919-6544; 1440-1789
• DOI: 10.1111/neup.12091

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 O6‐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.