Immunohistochemical Assessment of MGMT Expression and p53 Mutation in Glioblastoma Multiforme

作者: Jamal Shamsara , Sara Lary , Javad Behravan , Marziyeh Lotfi , Sima Afsharnezhad

DOI: 10.1177/030089161109700118

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摘要: ABSTRACT Aims and background. Theprognosisofglioblastomamultiforme(GBM)remainspoordespiteadvancesinsurgeryandadjuvanttherapies. TP53 andO6-methylgua -nine-DNAmethyltransferase( MGMT )aretumorsuppressorgenesthatareimplicat-edinGBMresistancetoradiationandchemotherapy.Inordertoassesstheexpres-sionoftheproteinproductsofthesetwogenes,50GBMsampleswereanalyzedinthisstudy.Methods.Demographicandclinicaldataalongwithpostsurgerytumorsamplesfrom50GBMpatientswerecollectedfromthepathologyarchive.MGMTandp53proteinexpressionwasevaluatedbyimmunohistochemistry.Results. 52%ofcaseshadmutatedp53,predominantlyexpressedinthenucleioftu -morcells.MGMTimmunohistochemistrywasnegativein35(70%)patientsandpos-itivein15(30%)others.Immunohistochemistry-negativespecimensforMGMTex -pressionshowedasignificantlyhigherexpressionofmutantp53( P = 0.03).Conclusion. MGMTexpressionwassignificantlylowerincellsbearingp53mutation.Thisindicatesthatthereisatendencyforp53activitytodeclinewithMGMTinacti-vation.However,thisstudycouldnotdeducewhichproteinwastheregulatoroftheother.Freefulltextavailableatwww.tumorionline.itIntroductionAmongthemostcommoncancersinIran,braintumorsrankeleventh.Glioblas-tomamultiforme(GBM)isthemostaggressiveandthemostprevalent,witha53%in -cidencerate

参考文章(31)
Gollin Sm, Pollack If, Hamilton Rl, Campbell Jw, Finkelstein Sd, Sherwin Rn, Bozik Me, Martinez Aj, The Relationship between TP53 Mutations and Overexpression of p53 and Prognosis in Malignant Gliomas of Childhood Cancer Research. ,vol. 57, pp. 304- 309 ,(1997)
Minoru Toyota, Manel Esteller, Stephen B. Baylin, Rosa Ana Risques, Victor Moreno, Miquel Angel Peinado, James G. Herman, Gabriel Capella, Promoter Hypermethylation of the DNA Repair Gene O6-Methylguanine-DNA Methyltransferase Is Associated with the Presence of G:C to A:T Transition Mutations in p53 in Human Colorectal Tumorigenesis Cancer Research. ,vol. 61, pp. 4689- 4692 ,(2001)
Peter J. Houghton, Joanna S. Remack, Linda C. Harris, Thomas P. Brent, Wild-Type p53 Suppresses Transcription of the Human O6-Methylguanine-DNA Methyltransferase Gene Cancer Research. ,vol. 56, pp. 2029- 2032 ,(1996)
Russell O. Pieper, Yuichi Hirose, Mitchel S. Berger, p53 Effects Both the Duration of G2/M Arrest and the Fate of Temozolomide-treated Human Glioblastoma Cells Cancer Research. ,vol. 61, pp. 1957- 1963 ,(2001)
Mirjam Hermisson, Andrea Klumpp, Wolfgang Wick, Jorg Wischhusen, Georg Nagel, Wynand Roos, Bernd Kaina, Michael Weller, O6‐methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells Journal of Neurochemistry. ,vol. 96, pp. 766- 776 ,(2006) , 10.1111/J.1471-4159.2005.03583.X
Gerd P. Pfeifer, p53 mutational spectra and the role of methylated CpG sequences Mutation Research. ,vol. 450, pp. 155- 166 ,(2000) , 10.1016/S0027-5107(00)00022-1
Dorothee Wiewrodt, Georg Nagel, Nadine Dreimüller, Thomas Hundsberger, Axel Perneczky, Bernd Kaina, MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome International Journal of Cancer. ,vol. 122, pp. 1391- 1399 ,(2008) , 10.1002/IJC.23219
Peter Birner, Maria Piribauer, Ingeborg Fischer, Brigitte Gatterbauer, Christine Marosi, Karl Ungersbock, Karl Rossler, Herbert Budka, Johannes Hainfellner, Prognostic relevance of p53 protein expression in glioblastoma. Oncology Reports. ,vol. 9, pp. 703- 707 ,(2002) , 10.3892/OR.9.4.703
Anthony E Pegg, Repair of O6-alkylguanine by alkyltransferases Mutation Research-reviews in Mutation Research. ,vol. 462, pp. 83- 100 ,(2000) , 10.1016/S1383-5742(00)00017-X
Christine Rolhion, Fr�d�rique Penault-Llorca, Jean-Louis Kemeny, Fabrice Kwiatkowski, Jean-Jacques Lemaire, Philippe Chollet, Fran�oise Finat-Duclos, Pierre Verrelle, O6-methylguanine-DNA methyltransferase gene (MGMT) expression in human glioblastomas in relation to patient characteristics and p53 accumulation International Journal of Cancer. ,vol. 84, pp. 416- 420 ,(1999) , 10.1002/(SICI)1097-0215(19990820)84:4<416::AID-IJC15>3.0.CO;2-A