Stereotactic image‑based histological analysis reveals a correlation between 11C‑methionine uptake and MGMT promoter methylation in non‑enhancing gliomas
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 me...
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Published in | Oncology letters Vol. 16; no. 2; pp. 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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AbstractList | 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. 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 11 C-methionine in positron-emission tomography (PET) reportedly reflects increased MGMT promoter methylation; however, non-stereotactic comparison of MGMT methylation and 11 C-methionine PET images may not be accurate. The present study examined the correlation between 11 C-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 11 C-methionine PET during pre-surgical examination. Clinical data were also collected from 3 patients during repeat surgery. The correlation between 11 C-methionine uptake and MGMT methylation or cell density was analyzed using histological specimens obtained by multiple stereotactic sampling and an exact local comparison of 11 C-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 11 C-methionine in PET may reflect increased MGMT promoter methylation according to stereotactic image-based histological analysis. 11 C-methionine PET could therefore be a useful tool for detecting regional MGMT promoter methylation in non-enhancing primary glioma. |
Author | Shofuda, Tomoko Kanematsu, Daisuke Fujinaka, Toshiyuki Yoshioka, Ema Kodama, Yoshinori Kanemura, Yonehiro Nonaka, Masahiro Okita, Yoshiko Nakajima, Shin Kinoshita, Manabu Mano, Masayuki |
AuthorAffiliation | 1 Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan 2 Division of Stem Cell Research, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan 5 Department of Central Laboratory and Surgical Pathology, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan 3 Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan 4 Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan 7 Department of Neurosurgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan 6 Department of Neurosurgery, Osaka International Cancer Institute, Chuo-ku, Osaka 541-8567, Japan |
AuthorAffiliation_xml | – name: 4 Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan – name: 7 Department of Neurosurgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan – name: 5 Department of Central Laboratory and Surgical Pathology, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan – name: 1 Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan – name: 2 Division of Stem Cell Research, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan – name: 3 Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan – name: 6 Department of Neurosurgery, Osaka International Cancer Institute, Chuo-ku, Osaka 541-8567, Japan |
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Cites_doi | 10.1158/0008-5472.CAN-11-0153 10.1111/j.1471-4159.1966.tb09884.x 10.1002/ijc.25229 10.1016/j.clineuro.2014.08.004 10.1177/0148607192016006569 10.1016/0022-510X(95)00117-K 10.3171/2014.9.FOCUS14521 10.1007/s11060-011-0737-8 10.1016/0020-708X(79)90049-8 10.3174/ajnr.A1008 10.3171/2010.11.JNS10553 10.1593/tlo.12253 10.1002/ijc.23219 10.1016/j.neuroimage.2009.11.024 10.1007/s00234-016-1758-y 10.1016/0883-2897(88)90077-3 10.1038/srep22477 10.1007/s11060-007-9486-0 10.3174/ajnr.A3173 10.1097/MNM.0000000000000236 10.1056/NEJMoa043331 10.1093/neuonc/nop050 10.1007/s00259-017-3618-3 10.1126/scitranslmed.3002693 10.1007/978-3-642-88516-7 10.1038/jcbfm.1990.123 10.3109/02841858709177339 10.1158/1078-0432.CCR-14-2737 10.1038/nm.2682 |
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Snippet | Gliomas are genetically and histopathologically heterogeneous. Intratumoral heterogeneity in the MGMT promoter methylation status is an important clinical... Gliomas are genetically and histopathologically heterogeneous. Intratumoral heterogeneity in the MGMT promoter methylation status is an important clinical... |
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StartPage | 1924 |
SubjectTerms | Brain cancer Chemotherapy Deoxyribonucleic acid DNA DNA methylation Glioma Medical imaging Mutation NMR Nuclear magnetic resonance Oncology Patients Surgery Tumors |
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Title | Stereotactic image‑based histological analysis reveals a correlation between 11C‑methionine uptake and MGMT promoter methylation in non‑enhancing gliomas |
URI | https://www.proquest.com/docview/2099297623 https://search.proquest.com/docview/2070808054 https://pubmed.ncbi.nlm.nih.gov/PMC6036429 |
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