Authors
1
Dept. of Pathology, Laboratories of Al-Imamain Al-Kadhumain Medical city, Baghdad, Iraq.
2
Dept. of Pathology and Forensic Medicine, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
,
Document Type : Research Paper
Abstract
BACKGROUND:
Gliomas are the most common primary malignant brain tumors in adults. They can occur anywhere in the central nervous system but primarily occur in the brain and arise in the glial tissue. O6-alkylguanine DNA alkyl transferase is a protein (DNA repair molecule) encoded by the O6-methylguanine DNA methyltransferase (MGMT) gene in human, and are able to remove alkyl adducts from the O6 position of guanine, and the O4 position of thymine, restoring these DNA bases and preventing temozolomide induced cell death.
OBJECTIVE:
To assess the immunohistochemical expression of MGMT in human glioma.
METHOD:
This retro and prospective study included 56 tissue paraffin blocks of intracranial gliomas assigned as cases group, and 28 tissue paraffin blocks of normal brain tissue as control group. From each block, two sections were taken; one was stained with the routine hematoxylin and eosin stain, and the other was stained immunohistochemically for marker MGMT.
RESULTS:
MGMT showed a highly significant difference in its expression between the control group and the disease group (p value<0.001). MGMT showed a highly significant relation between its expression and the age of patients with glioma (p value< 0.001). MGMT expression showed no significant correlation with other clinicopathological parameters like the histological types and gender (p value CONCLUSION:
MGMT revealed a highly significant difference inits expression in brain tumors (gliomas) compared to control groupwhich mayreflects the need in proliferating cells for greater capacity to repair O6-alkylguanineadducts before replication. Besides there was a significant correlation between age and MGMT expression which may reflect processes associated with the physical and functional maturation of the CNS during life.
- 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. ActaZ Neuropathol. 2016;131:803–20.
- Banan R, Hartmann C. The new WHO 2016 classification of brain tumors—what neurosurgeons need to know. Acta Neurochirurgica. 2017.
- Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006 - 2010. J Neurooncol. 2013;15:788–96.
- Board IC. Annual Report Iraqi Cancer Registry. 2015;
- Cancer Council Australia. Adult gliomas (astrocytomas and oligodendrogliomas): a guide for patients, their families and carers. 2011; Available from: zhttp://www.cancer.org.au/content/pdf/HealthProfessionals/ClinicalGuidelines/Adult_Glioma_Consumer_Guide_FINAL_bookmarked.pdf
- Barnholtz-Sloan JS, Ostrom QT, Cote D. Epidemiology of Brain Tumors. Neurologic Clinics. 2018.
- Baldi I, Engelhardt J, Bonnet C, Bauchet L, Berteaud E, Grüber A, et al. Épidémiologie Des Méningiomes. Neurochirurgie [Internet]. 2018;64:5–14. Available from: https://doi.org/10.1016/j.neuchi.2014.05.006
- Schmitt AM, Pavel M, Rudolph T, Dawson H, Blank A, Komminoth P, et al. Prognostic and predictive roles of MGMT protein expression and promoter methylation in sporadic pancreatic neuroendocrine neoplasms. Neuroendocrinology. 2014;100:35–44.
- Kdolsky RK, Gibbons DF, Kwasny O, Schabus R, Plenk H. J, Zeman P, et al. ABSTRACTS. Am J Sports Med. 2016;
- Baran K, Yang M, Dillon CP, Samson LL, Green DR. The proline rich domain of p53 is dispensable for MGMT-dependent DNA repair and cell survival following alkylation damage. 2017;24:1925–36. Available from: http://dx.doi.org/10.1038/cdd.2017.116
- Fahrer J, Kaina B. Review O 6 -methylguanine-DNA methyltransferase in the defense against N -nitroso compounds and colorectal cancer. 2013;34:2435–42.
- Fu D, Calvo JA, Samson LD. Balancing repair and tolerance of DNA damage caused by alkylating agents. 2012;12(February).
- Christmann M, Kaina B. O 6-methylguanine-DNA methyltransferase (MGMT): Impact on cancer risk in response to tobacco smoke. Mutat Res - Fundam Mol Mech Mutagen [Internet]. 2012;736:64–74. Available from: http://dx.doi.org/10.1016/j.mrfmmm.2011.06.004
- Christmann M, Nagel G, Horn S, Krahn U, Wiewrodt D, Sommer C, et al. MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: A comparative study on astrocytoma and glioblastoma. Int J Cancer. 2010;127:2106–18.
- Christmann M, Verbeek B, Roos WP, Kaina B. Biochimica et Biophysica Acta O 6 -Methylguanine-DNA methyltransferase ( MGMT ) in normal tissues and tumors : Enzyme activity , promoter methylation and immunohistochemistry. BBA - Rev Cancer [Internet]. 2011;1816:179–90. Available from: http://dx.doi.org/10.1016/j.bbcan.2011.06.002
- Pollack IF, Hamilton RL, Sobol RW, Burnham J, Yates AJ, Holmes EJ, et al. O6-Methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: Results from the CCG-945 cohort. J Clin Oncol. 2006;24:3431–7.
- Pandith AA, Qasim I, Zahoor W, Shah P, Bhat AR, Sanadhya D, et al. Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide). Sci Rep [Internet]. 2018;8:1–11. Available from: http://dx.doi.org/10.1038/s41598-018-25169-2
- Li Q, Guo J, Wang W, Wang D. Relationship between MGMT gene expression and treatment effectiveness and prognosis in glioma. Oncol Lett. 2017;14:229–33.
- Horbinski C, Hamilton RL, Lovell C, Burnham J, Pollack IF. Impact of morphology, MIB-1, p53 and MGMT on outcome in pilocytic astrocytomas. Brain Pathol. 2010;
- 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. Oncol Lett. 2013;
- Brell M, Tortosa A, Verger E, Gil JM, Viñolas N, Villá S, et al. Prognostic Significance of O 6 -Methylguanine-DNA Methyltransferase Determined by Promoter Hypermethylation and Immunohistochemical Expression in Anaplastic Gliomas Determined by Promoter Hypermethylation and Immunohistochemical. Clin cancer Res. 2005;11:5167–74.
- Rodriguez FJ, Thibodeau SN, Jenkins RB, Schowalter K V., Caron BL, OʼNeill BP, et al. MGMT Immunohistochemical Expression and Promoter Methylation in Human Glioblastoma. Appl Immunohistochem Mol Morphol [Internet]. 2007;PAP:59–65. Available from: https://insights.ovid.com/crossref?an=00129039-900000000-99992
- Ogura R, Tsukamoto Y, Natsumeda M, Isogawa M, Aoki H, Kobayashi T, et al. Immunohistochemical profiles of IDH1, MGMT and P53: Practical significance for prognostication of patients with diffuse gliomas. Neuropathology. 2015;
- Lotfi M, Afsharnezhad S, Raziee HR, Ghaffarzadegan K, Sharif S, Shamsara J, et al. Immunohistochemical assessment of MGMT expression and p53 mutation in glioblastoma multiforme. Tumori. 2011;
- 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.
- Li X, Wei J, Liu Y, Li P, Fan L, Wang Y, et al. Primary Astrocytic Tumours and Paired Recurrences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss. Sci Rep. 2017;
- Preuss I, Eberhagen I, Haas S, Eibl RH, Kaufmann M, Minckwitz G Von, et al. O6‐methylguanine‐DNA methyltransferase activity in breast and brain tumors. Int J Cancer. 1995;61:321–6.
- Bobola MS, Berger MS, Ellenbogen RG, Roberts TS, Geyer JR, Silber JR. O6-methylguanine-DNA methyltransferase in pediatric primary brain tumors: Relation to patient and tumor characteristics. Clin Cancer Res. 2001;
- Shah N, Lin B, Sibenaller Z, Ryken T, Lee H, Yoon JG, et al. Comprehensive analysis of MGMT promoter methylation: Correlation with MGMT expression and clinical response in GBM. PLoS One. 2011;6.
- Miyazaki M, Nishihara H, Terasaka S, Kobayashi H, Yamaguchi S, Ito T, et al. Immunohistochemical evaluation of O 6 -methylguanine DNA methyltransferase ( MGMT ) expression in 117 cases of glioblastoma. 2014;(November 2013):268–76.
- Mellai M, Caldera V, Annovazzi L, Chiò A, Lanotte M, Cassoni P, et al. MGMT promoter hypermethylation in a series of 104 glioblastomas. Cancer Genomics and Proteomics. 2009;6:219–27.