Stereotactic image-based histological analysis reveals a correlation between C-methionine uptake and promoter methylation in non-enhancing gliomas.

Gliomas are genetically and histopathologically heterogeneous. Intratumoral heterogeneity in the promoter methylation status is an important clinical biomarker of glioblastoma. A higher uptake of C-methionine in positron-emission tomography (PET) reportedly reflects increased promoter methylation; however, non-stereotactic comparison of methylation and C-methionine PET images may not be accurate. The present study examined the correlation between C-methionine uptake and 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 C-methionine PET during pre-surgical examination. Clinical data were also collected from 3 patients during repeat surgery. The correlation between C-methionine uptake and methylation or cell density was analyzed using histological specimens obtained by multiple stereotactic sampling and an exact local comparison of 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 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 methylation (R=0.01, P=0.97) or cell density (R=0.15, P=0.70). An increased uptake of C-methionine in PET may reflect increased promoter methylation according to stereotactic image-based histological analysis. C-methionine PET could therefore be a useful tool for detecting regional promoter methylation in non-enhancing primary glioma.