Intratumoral and Peritumoral Apparent Diffusion Coefficient and MGMT mRNA Expression in Different Meningioma Histopathological Grade

Rahmad Mulyadi, Mochamma Hatta, Andi Asadul Islam, Bachtiar Murtala, Jumraini Tammase, Muhammad Firdaus, Eka Susanto, Joedo Prihartono


BACKGROUND: Histopathological examination is the gold standard for diagnosing meningioma and determining the treatments. However, it is invasive in nature. This study was conducted to identify intratumoral and peritumoral apparent diffusion coefficient (ADC) value and mRNA O6-methylguanine-DNA methyltransferase (MGMT) expression in meningioma.

METHODS: Data were collected from 39 patients who were clinically diagnosed with meningioma. However, only 37 patients met the inclusion criteria. These subjects then underwent examinations and received treatment from October 2017 to September 2018. Magnetic resonance imaging (MRI) data with diffusion-weighted imaging-apparent diffusion coefficient (DWI-ADC) sequence, histopathological diagnosis of meningioma, and results of MGMT mRNA expression were obtained.

RESULTS: The most frequent type of low-grade and overall tumor was meningioma not otherwise specified (56.8%). For high-grade tumor, there were two atypical cases: atypical meningioma (2.7%) and rhabdoid meningioma (2.7%). Meningothelial meningioma had the highest mean value of minimum intratumoral ADC at 864.57±219 x10-3 mm2/s, whereas rhabdoid meningioma had the lowest at 417 x10-3 mm2/s. For minimum peritumoral ADC, rhabdoid meningioma had the highest mean value at 1,651 x10-3 mm2/s, while atypical meningioma has the lowest at 1,281 x10-3 mm2/s. For MGMT mRNA, meningothelial meningioma had the highest mean value at 10±1.2 fold change, whereas rhabdoid meningioma had the lowest mean at 6.18 fold change.

CONCLUSION: WHO grade I meningiomas had higher minimum intratumoral ADC values and higher MGMT mRNA expression than the high-grade tumors. Minimum peritumoral ADC values differed across the histopathological grades.

KEYWORDS: meningioma, RNA, messenger, MRI, methyltransferases, RT-PCR, ADC, MGMT mRNA

Full Text:



Baldi I, Engelhardt J, Bonnet C, Bauchet L, Berteaud E, Grüber A, et al. Epidemiology of meningiomas. Neurochirurgie. 2018; 64: 5-14, CrossRef.

Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol. 2018; 20 (Suppl 4): iv1-iv86, CrossRef.

Watts J, Box G, Galvin A, Brotchie P, Trost N, Sutherland T. Magnetic resonance imaging of meningiomas: a pictorial review. Insights Imaging. 2014; 5: 113-22, CrossRef.

Villanueva-Meyer JE, Mabray MC, Cha S. Current clinical brain tumor imaging. Neurosurgery. 2017; 81: 397-415, CrossRef.

Tamrazi B, Shiroishi MS, Liu CSJ. Advanced imaging of intracranial meningiomas. Neurosurg Clin N Am. 2016; 27: 137-43, CrossRef.

Staedtke V, Dzaye OD, Holdhoff M. Actionable molecular biomarkers in primary brain tumors. Trends Cancer. 2016; 2: 338-49, CrossRef.

Ueda S, Mineta T, Nakahara Y, Okamoto H, Shiraishi T, Tabuchi K. Induction of the DNA repair gene O6-methylguanine—DNA methyltransferase by dexamethasone in glioblastomas. J Neurosurg. 2004; 101: 659-63, CrossRef.

Panagopoulos I, Gorunova L, Leske H, Niehussman P, Johannessen LE, Staurseth J, et al. Pyrosequencing analysis of MGMT promoter methylation in meningioma. Cancer Genom Proteom. 2018; 15: 379-85, CrossRef.

Kreth S, Thon N, Eigenbrod S, Lutz J, Ledderose C, Egensperger R, et al. O6-methylguanine-DNA methyltransferase (MGMT) mRNA expression predicts outcome in malignant glioma independent of MGMT promoter methylation. PLoS One. 2011; 6: e17156, CrossRef.

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016; 131: 803-20, CrossRef.

Tambaip T, Br Karo M, Hatta M, Dwiyanti R, Natzir R, Nasrum Mas M, et al. Immunomodulatory effect of orally red fruit (Pandanus conoideus) extract on the expression of CC chemokine receptor 5 mRNA in HIV patients with antiretroviral therapy. Res J Immunol. 2018; 11: 15-21, CrossRef.

Sirait RH, Hatta M, Ramli M, Islam AA. Systemic lidocaine inhibits high‑mobility group box 1 messenger ribonucleic acid expression and protein in BALB/c mice after closed fracture musculoskeletal injury. Saudi J Anesth. 2018; 12: 395-8, CrossRef.

Jabini R, Moradi A, Afsharnezhad S, Ayatollahi H, Behravan J, Raziee HR, et al. Pathodiagnostic parameters and evaluation of O 6 - methyl guanine methyl transferase gene promoter methylation in meningiomas. Gene. 2014; 538: 348-53, CrossRef.

Larijani L, Madjd Z, Samadikuchaksaraei A, Younespour S, Zham H, Rakhshan A, et al. Methylation of O 6-methyl guanine methyltransferase gene promoter in meningiomas - comparison between tumor grades I, II, and III. Asian Pacific J Cancer Prev. 2014; 15: 33-8, CrossRef.

Van Alkemade H, De Leau M, Dieleman EMT, Kardaun JWPF, Van Os R, Vandertop WP, et al. Impaired survival and long-term neurological problems in benign meningioma. Neuro Oncol. 2012; 14: 658-66, CrossRef.

Surov A, Ginat DT, Sanverdi E, Lim CCT, Hakyemez B, Yogi A, et al. Use of diffusion weighted imaging in differentiating between malignant and benign meningiomas: a multicenter analysis. World Neurosurg. 2016; 88: 598-602, CrossRef.

Watanabe Y, Yamasaki F, Kajiwara Y, Takayasu T, Nosaka R, Akiyama Y, et al. Preoperative histological grading of meningiomas using apparent diffusion coefficient at 3T MRI. Eur J Radiol. 2013; 82: 658-63, CrossRef.

Toh CH, Castillo M, Wong AMC, Wei KC, Wong HF, Ng SH, et al. Differentiation between classic and atypical meningiomas with use of diffusion tensor imaging. Am J Neuroradiol. 2008; 29: 1630-5, CrossRef.

Abdel-Kerim A, Shehata M, El Sabaa B, Fadel S, Heikal A, Mazloum Y. Differentiation between benign and atypical cranial Meningiomas. Can ADC measurement help? MRI findings with histopathological correlation. Egypt J Radiol Nucl Med. 2018; 49: 172-5, CrossRef.

Lu Y, Liu L, Luan S, Xiong J, Geng D, Yin B. The diagnostic value of texture analysis in predicting WHO grades of meningiomas based on ADC maps: an attempt using decision tree and decision forest. Eur Radiol. 2019; 29: 1318-28, CrossRef.

Santelli L, Ramondo G, Della Puppa A, Ermani M, Scienza R, D’Avella D, et al. Diffusion-weighted imaging does not predict histological grading in meningiomas. Acta Neurochir (Wien). 2010; 152: 1315-9, CrossRef.

Sanverdi SE, Ozgen B, Oguz KK, Mut M, Dolgun A, Soylemezoglu F, et al. Is diffusion-weighted imaging useful in grading and differentiating histopathological subtypes of meningiomas? Eur J Radiol. 2012; 81: 2389-95, CrossRef.

Provenzale JM, McGraw P, Mhatre P, Guo AC, Delong DM. Peritumoral brain regions in gliomas and meningiomas: Investigation with isotropic diffusion-weighted MR imaging and diffusion-tensor MR imaging. Radiology. 2004; 232: 451-60, CrossRef.

Hwang WL, Marciscano AE, Niemierko A, Kim DW, Stemmer-Rachamimov AO, Curry WT, et al. Imaging and extent of surgical resection predict risk of meningioma recurrence better than WHO histopathological grade. Neuro Oncol. 2016; 18: 863-72, CrossRef.

Everson RG, Hashimoto Y, Freeman JL, Hodges TR, Huse J, Zhou S, et al. Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design. J Neurooncol. 2018; 139: 469-78, CrossRef.

Chang IW, Lin JW, Wu YT. The status of MGMT protein expression is a prognostic factor for meningeal hemangiopericytoma: a clinicopathologic and immunohistochemical study of 12 cases at a single institution. J Neurooncol. 2011; 105: 563-72, CrossRef.

Bello MJ, Amiñoso C, Lopez-Marin I, Arjona D, Gonzalez-Gomez P, Alonso ME, et al. DNA methylation of multiple promoter-associated CpG islands in meningiomas: relationship with the allelic status at 1p and 22q. Acta Neuropathol. 2004; 108: 413-21, CrossRef.

Aydemir F, Yurtcu E, Balci TB, Sahin FI, Gulsen S, Altinors N. Identification of promoter region methylation patterns of MGMT, CDKN2A, GSTP1, and THBS1 genes in intracranial meningioma patients. Genet Test Mol Biomarkers. 2012; 16: 335-40, CrossRef.

Drabycz S, Roldán G, de Robles P, Adler D, McIntyre JB, Magliocco AM, et al. An analysis of image texture, tumor location, and MGMT promoter methylation in glioblastoma using magnetic resonance imaging. Neuroimage. 2010; 49: 1398-405, CrossRef.

Moon WJ, Choi JW, Roh HG, Lim SD, Koh YC. Imaging parameters of high grade gliomas in relation to the MGMT promoter methylation status: the CT, diffusion tensor imaging, and perfusion MR imaging. Neuroradiology. 2012; 54: 555-63, CrossRef.

Romano A, Calabria LF, Tavanti F, Minniti G, Rossi-Espagnet MC, Coppola V, et al. Apparent diffusion coefficient obtained by magnetic resonance imaging as a prognostic marker in glioblastomas: correlation with MGMT promoter methylation status. Eur Radiol. 2013; 23: 513-20, CrossRef.

Gupta A, Omuro AMP, Shah AD, Graber JJ, Shi W, Zhang Z, et al. Continuing the search for MR imaging biomarkers for MGMT promoter methylation status: conventional and perfusion MRI revisited. Neuroradiology. 2012; 54: 641-3, CrossRef.


Copyright (c) 2021 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute