Stereotactic image‑based histological analysis reveals a correlation between 11C‑methionine uptake and MGMT promoter methylation in non‑enhancing gliomas

Okita,Yoshiko; Shofuda,Tomoko; Kanematsu,Daisuke; Yoshioka,Ema; Kodama,Yoshinori; Mano,Masayuki; Kinoshita,Manabu; Nonaka,Masahiro; Nakajima,Shin; Fujinaka,Toshiyuki; Kanemura,Yonehiro

doi:10.3892/ol.2018.8866

Stereotactic image‑based histological analysis reveals a correlation between 11C‑methionine uptake and MGMT promoter methylation in non‑enhancing gliomas

Authors:
- Yoshiko Okita
- Tomoko Shofuda
- Daisuke Kanematsu
- Ema Yoshioka
- Yoshinori Kodama
- Masayuki Mano
- Manabu Kinoshita
- Masahiro Nonaka
- Shin Nakajima
- Toshiyuki Fujinaka
- Yonehiro Kanemura
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Affiliations: Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Chuo‑ku, Osaka 540‑0006, Japan, Division of Stem Cell Research, Osaka National Hospital, National Hospital Organization, Chuo‑ku, Osaka 540‑0006, Japan, Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Chuo‑ku, Osaka 540‑0006, Japan, Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kamigyo‑ku, Kyoto 602‑8566, Japan, Department of Central Laboratory and Surgical Pathology, Osaka National Hospital, National Hospital Organization, Chuo‑ku, Osaka 540‑0006, Japan, Department of Neurosurgery, Osaka International Cancer Institute, Chuo‑ku, Osaka 541‑8567, Japan, Department of Neurosurgery, Kansai Medical University, Hirakata, Osaka 573‑1010, Japan
Published online on: May 31, 2018 https://doi.org/10.3892/ol.2018.8866
Pages: 1924-1930

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Abstract

Gliomas are genetically and histopathologically heterogeneous. Intratumoral heterogeneity in the MGMT promoter methylation status is an important clinical biomarker of glioblastoma. A higher uptake of 11C‑methionine in positron‑emission tomography (PET) reportedly reflects increased MGMT promoter methylation; however, non‑stereotactic comparison of MGMT methylation and 11C‑methionine PET images may not be accurate. The present study examined the correlation between 11C‑methionine uptake and MGMT promoter methylation in non‑enhancing gliomas using stereotactic image‑based histological analysis. Data were collected from 9 patients with newly diagnosed non‑enhancing glioma who underwent magnetic resonance imaging and 11C‑methionine PET during pre‑surgical examination. Clinical data were also collected from 3 patients during repeat surgery. The correlation between 11C‑methionine uptake and MGMT methylation or cell density was analyzed using histological specimens obtained by multiple stereotactic sampling and an exact local comparison of 11C‑methionine PET images and histological specimens was made. A total of 31 stereotactic sample sites were identified. In newly diagnosed cases, the tumor to normal uptake (T/N) ratio revealed a significant positive correlation with MGMT methylation (R=0.54, P=0.009) and a marginal correlation with cell density (R=0.42, P=0.05). In recurrent cases, the T/N ratio demonstrated no correlation with MGMT methylation (R=0.01, P=0.97) or cell density (R=0.15, P=0.70). An increased uptake of 11C‑methionine in PET may reflect increased MGMT promoter methylation according to stereotactic image‑based histological analysis. 11C‑methionine PET could therefore be a useful tool for detecting regional MGMT promoter methylation in non‑enhancing primary glioma.

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