Issue

Vol. 66 No. 5: Issue 5

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Immunohistochemical expression of MGMT in Gliomas

https://doi.org/10.14715/cmb/2020.66.5.4
Jalal Ali Jalal
Department of Basic Sciences Pathology, College of Medicine, Hawler Medical University, Erbil, Kurdistan Region- Iraq.

Corresponding Author(s) : Jalal Ali Jalal

jajpishdary@gmail.com

Cellular and Molecular Biology, Vol. 66 No. 5: Issue 5

Abstract

Glioma is one of the main tumors of the central nervous system occurring in the spinal cord or brain, and is the origin of glioma tumors. The most common site of glioma is the brain. Glioma accounts for 30% of all central nervous system tumors and 80% of malignant brain tumors. O6-methylguanine-DNA methyltransferase (MGMT) gene mutations have been identified in many human cancers including gliomas. This study aimed to evaluate the immune expression of MGMT in different gliomas and its relationship with different clinicopathological parameters. From January 2015 to January 2017, 97 cases of glioma were retrieved from the Rizgary Pathology Center in Erbil-Iraq. The tumors were typed and graded according to the 2007 World Health Organization Brain Tumor Classification. Immunohistochemical staining was done for MGMT using monoclonal Antibodies via the automated immunostainer technique. Positive MGMT immunoexpression was observed in 60 (61.9%) cases. Significantly high rates of MGMT immunoexpression were demonstrated among the 2 age groups: 45-54 years and 25-34 years (23.3% and 21.7% respectively). Most positive cases were observed among the supratentorial tumors (81.7%) and dominant grade IV gliomas (48.4%) with no significant association. Immunohistochemically, MGMT is frequently expressed in gliomas particularly in glioblastomas with bimodal age association.

Keywords

Glioma MGMT Immunohistochemistry
Jalal, J. A. (2020). Immunohistochemical expression of MGMT in Gliomas. Cellular and Molecular Biology, 66(5), 20–24. https://doi.org/10.14715/cmb/2020.66.5.4
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds. WHO classification of tumours of the central nervous system. 4th ed. Lyon, France: IARC Press 2007.
  2. Burger PC, Scheithauer BW, Paulus W, Szymas J, Giannini C, Kleihues P, Cavenee WK. Pilocytic astrocytoma. In: Kleihues P, Cavenee WK, eds. Pathology and genetics of tumours of the nervous system. Lyon, France: IARC Press 2000; 45-51.
  3. Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:987-96.
  4. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008; 359:492-507.
  5. Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and followup. Annals of Oncol 2014; 25 Suppl 3:iii93-101.
  6. Nakagawachi T, Soejima H, Urano T, Zhao W, Higashimoto K, Satoh Y, Matsukura S, Kudo S, Kitajima Y, Harada H, Furukawa K, Matsuzaki H, Emi M, Nakabeppu Y, Miyazaki K, Sekiguchi M, Mukai T. Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer. Oncogene 2003; 22:8835–8844.
  7. Everhard S, Kaloshi G, Criniere E, Benouaich-Amiel A, Lejeune J, Marie Y, Sanson M, Kujas M, Mokhtari K, Xuan KH, Yves Delattre J, Thillet J. MGMT methylation: a marker of response to temozolomide in low-grade gliomas. Ann Neurol 2006; 60:740– 743.
  8. Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA, Muzikansky A, Santagata S, L Ligon K, D Norden A, Ciampa A, Bradshaw J, Levy B, Radakovic G, Ramakrishna N, Black P. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 2009; 15:330–337.
  9. Komine C, Watanabe T, Katayama Y, Yoshino A, Yokoyama T, Fukushima T. Promoter hypermethylation of the DNA repair gene O6-methylguanine-DNA methyltransferase is an independent predictor of shortened progression free survival in patients with low-grade diffuse astrocytomas. Brain Pathol 2003; 13:176–184.
  10. Hegi ME, Diserens AC, Godard S. Clinical trial substantiates the predictive value of O6 -methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 2004; 10:1871–1874.
  11. Hegi ME, Diserens AC, Gorlia T. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352:997–1003 5.
  12. Olson RA, Brastianos PK, Palma DA. Prognostic and predictive value of epigenetic silencing of MGMT in patients with high grade gliomas: a systematic review and meta-analysis. J Neurooncol 2011; 105:325–335.
  13. Tosoni A, Franceschi E, Ermani M, Bertorelle R, Bonaldi L, Blatt V, Brandes AA. Temozolomide three weeks on and one week off as first line therapy for patients with recurrent or progressive low grade gliomas. J Neurooncol 2008; 89:179–185 22.
  14. Capper D, Mittelbronn M, Meyermann R, Schittenhelm J. Pitfalls in the assessment of MGMT expression and in its correlation with survival in diffuse astrocytomas: proposal of a feasible immunohistochemical approach. Acta Neuropathol 2008; 115: 249–59.
  15. Lechapt-Zalcman E, Levallet G, Dugue AE, Vital A, Diebold M, Menei P. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and low MGMT-encoded protein expression as prognostic markers in glioblastoma patients treated with biodegradable carmustine wafer implants after initial surgery followed by radiotherapy with concomitant and adjuvant temozolomide. Am Cancer Soc 2012; 118: 4545–54.
  16. Younis SG, Khedr RA, El- Shorbagy SH. Immunohistochemical analysis of
  17. O6-methylguanine-DNA methyltransferase (MGMT) protein expression as prognostic marker in glioblastoma patients treated with radiation therapy with concomitant and adjuvant Temozolomide. J Egypt Natl Canc Inst 2016; 28: 23–30.
  18. Al Hasnawi SM, Al Mosawi AJ, Al Khzaie A, Unan OF, Fadhil HM, Sami S. Cancer in Iraq: Distribution by primary tumor site. N Iraqi J Med 2009; 5 (1): 5- 8.
  19. Zhu Z, Du S, Ding F, Guo S, Ying G, Yan Z. Ursolic acid attenuates temozolomide resistance in glioblastoma cells by downregulating O (6) methylguanine DNA methyltransferase (MGMT) expression. Am J Transl Res 2016; 8 (7): 3299–308.
  20. Cankovic M, Nikiforova MN, Snuderl M, Adesina AM, Lindeman N, Wen PY, Leek EQ. The Role of MGMT Testing in Clinical Practice a Report of the Association for Molecular Pathology. JMD 2013; 15, 5: 539-55.
  21. Brell M, Tortosa A, Verger E, Gil EM, Vinolas N, Villa S. Prognostic Significance of O6 -Methylguanine-DNA Methyltransferase Determined by Promoter Hypermethylation and Immunohistochemical Expression in Anaplastic Gliomas. Clin Cancer Res 2005; 11:5167-5174.
  22. Nakasu S, Fukami T, MD, Jyunya Jito, MD, Masayuki Matsuda, Prognostic significance of loss of O6 -methylguanine-DNA methyltransferase expression in supratentorial diffuse low-grade astrocytoma. Surg Neurol 2007; 68: 603 – 609.
  23. Christmann M, Nagel G, Horn S, Krahn U, Wiewrodt D, Sommer C, Kaina B. MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and glioblastoma. Int J Cancer 2010; 127, 2106–2118.
  24. Groenendijk FH, Taal W, Dubbink HJ, Haarloo CR, Kouwenhoven MC, van den Bent MJ, Kros JM, Dinjens WN. MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation. J Neurooncol 2011; 101:405–417.
  25. Mellai M, Monzeglio O, Piazzi A, Caldera V, Annovazzi L, Cassoni P, Valente G, Cordera S, Mocellini C, Schiffer D. MGMT promoter hypermethylation and its associations with genetic alterations in a series of 350 brain tumors. J Neurooncol 2012; 107(3):617-31.
  26. Hu X, Miao W, Zou Y, Zhang W, Zhang Y, Liu H. Expression of p53, epidermal growth factor receptor, Ki-67 and O6 -methylguanine-DNA methyltransferase in human gliomas. Oncology Letters 2013; 6: 130-134.
  27. Ogura R, Tsukamoto Y, Natsumeda M, Isogawa M, Aoki H, Kobayashi T, Yoshida S, Okamoto K, Takahashi H, Fujii Y, Kakita A. Immunohistochemical profiles of IDH1, MGMT and P53: Practical significance for prognostication of patients with diffuse gliomas. Neuropathol 2015; 35, 324–335.
  28. Gepp RA, Rocque AL, Martins BJFA, Batista GR, Farage L, Pratesi R. Prognostic Analysis in Malignant Gliomas: Relationship between Brain Perfusion Magnetic Resonance and Methylation Analysis of MGMT Gene Promoter. Austin Neurosurg Open Access 2016; 3(2): 1053.
  29. Megova M, Drabek J, Dwight Z, Trojanec R, Koudelakova V, Vrbkova J, Kalita O, Mlcochova S, Rabcanova M, Hajduch M. Isocitrate Dehydrogenase Mutations are Better Prognostic Marker than O6 -methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastomas – a Retrospective, Single-centre Molecular Genetics Study of Gliomas. Clin Oncol 2017; 30(5): 361–371.
  30. Pandith AA, Qasim I, Zahoor W, Shah P, Bhat AR, Sanadhya D, Shah ZA, Naikoo NA. Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide). Sci Rep 2018; 8:6704 | DOI: 10.1038/s41598-018-25169-2.
  31. Shah N, Lin B, Sibenaller Z, Ryken T, Lee H, Yoon JG, Rostad S, Foltz G. Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM. PLoS One 2011; 7: 6(1):e16146.
  32. Molenaar RJ, Verbaan D, Lamba S, Zanon C, Jeuken JWM, Boots-Sprenger SHE. The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone. Neuro Oncol 2014; 16(9), 1263–1273.
  33. Anvari K, Toussi MS, Ayatollahi H, Bahadorkhan G, Nasiri MG, Ersi MF. Prognostic Significance of MGMT Promoter Methylation in Patients with Glioblastoma Undergoing Surgical Intervention: A Retrospective Study in Northeastern Iran. Middle East J Cancer 2018; 9(3): 179-185.
  34. Abdel Moneim R, Abdel-Rafei M, Hassan H, El-Zawahry I, Hashem W. Prognostic Significance of MGMT Promoter Methylation in Egyptian GBM Patients: a Single-institution Experience. Asian Pac J Cancer Biol 2018; 3 (1), 1-4.
  35. Lotfi M, Afsharnezhad S, Raziee HR, Ghaffarzadegan K, Sharif S, Shamsara J, Lary S, Behravan J.Immunohistochemical assessment of MGMT expression and p53 mutation in glioblastoma multiforme. Tumori 2011; 97: 104-108.
  36. Wang K, Wang Y, Ma J, WangJ, Li S, Jiang T, Dai J. Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation. Asian Pac J Cancer Prev 2014; 15 (24), 10893-10898.
  37. Pan Q, Yang X, Zhu L, Song C, Diao X, Gao Y, Zhu J, Yue X, Li H, Cheng W, Ning Y. Heterogeneity of MGMT gene promoter methylation and protein expression in serial specimens in newly diagnosed glioblastoma. Int J Clin Exp Med 2016; 9(9):17356-17366.
  38. Nakasu S, Fukami T, Jito J, Matsuda M. Prognostic significance of loss of O6 -methylguanine-DNA methyltransferase expression in supratentorial diffuse low-grade astrocytoma. Surg Neurol 2007; 68, 603 – 609.
  39. Sippl C, Urbschat S, Kim YJ, Senger S, Oertel J, Ketter R. Promoter methylation of RB1, P15, P16, and MGMT and their impact on the clinical course of pilocytic astrocytomas. Oncol Lett 2018; 15: 1600-1606.
  40. Sardi I, Cetica V, Massimino M, Buccoliero AM, Giunti L, Genitori L, Arico M. Promoter methylation and expression analysis of MGMT in advanced pediatric brain tumors. Oncol Rep 2009; 22: 773-779.
  41. Gramatzki D, Roth P, Felsberg J, Hofer S, Rushing EJ, Hentschel B, Westphal M, Krex D, Simon M, Schnell O, Wick W. Chemotherapy for intracranial ependymoma in adults. BMC Cancer 2016; 16:287.
  42. Kazemi E, Kahrizi D. Lack of association between gastric cancer and hopq alleles in Helicobacter pylori. Genetika 2016; 48(3): 893-902
  43. Kazemi E, Kahrizi D, Moradi MT, Sohrabi M, Yari K. Gastric Cancer and Helicobacter pylori: Impact of hopQII Gene. Cell Mol Biol 2016; 62(2): 107-110.
  44. Kazemi E, Kahrizi D, Moradi MT, Sohrabi M, Amini A, Mousavi SAR, Yari K. Association between Helicobacter pylori hopQI genotyping and human gastric cancer. Cell Mol Biol 2016; 62(1): 6-9.
  45. Kazemi E, Kahrizi D, Moradi MT, Sorabi, M, Amini S, Mousavi S.A.R., Yari K. Association between Manganese Superoxide Dismutase (MnSOD Val-9Ala) genotypes with the risk of generalized aggressive periodontitis disease. Cell Mol Biol 2016; 61 (8): 49-52.
  46. Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.
  47. Sohan Forooshan Moghadam A, Ataei M, Arabzadeh G, Falahati K, Roshani F, Sanati M H. Analysis of MicroRNA-18a Expression in Multiple Sclerosis Patients. rbmb.net 2020; 8 (4) :429-437.
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download this PDF file
PDF
Statistic
Read Counter : 833 Download : 436

Most read articles by the same author(s)